Environmental enrichment decreases responding for visual novelty

Previous research has demonstrated that rats reared in an enriched condition (EC) with novel objects and social partners self-administer less amphetamine compared to rats raised in an isolated condition (IC). However, it is unclear if the enrichment-induced decrease in stimulant self-administration generalizes to non-drug rewards such as those provided by novel environmental stimuli. In the current study, EC, IC, and social condition (SC) rats were raised from 21 to 51 days of age before being tested in a two-lever operant conditioning chamber in which responding on one lever (active lever) resulted in illumination of a cue light. In Experiment 1, rats were initially assessed for baseline responding (no contingency) and then the contingent light was introduced. EC rats responded less than IC rats for the contingent light stimulus; however, EC rats also displayed a lower rate of baseline responding. In Experiment 2, rats were trained initially to lever press for a sucrose reward to decrease differences in baseline responding. While sucrose pretraining decreased baseline response differences between groups, EC rats still responded less for the contingent light stimulus than IC or SC rats. These results suggest that environmental enrichment decreases the incentive value of visual novelty.     

Rapid stimulus-bound suppression of intake in response to an intraduodenal nonnutritive sweetener after training with nutritive sugars predicting malaise

In a previous report (Schier et al., Am J Physiol Regul Integr Comp Physiol 301: R1557-R1568, 2011), we demonstrated with a new behavioral procedure that rats exhibit stimulus-bound suppression of intake in response to an intraduodenal (ID) bitter tastant predicting subsequent malaise. With the use of the same modified taste aversion procedure, the present experiments evaluated whether the sweet taste properties of ID stimuli are likewise detected and encoded. Thirsty rats licked at sipper spouts for hypotonic NaCl for 30 min and received brief (first 6 min) yoked ID infusions of either the same NaCl or an isomolar lithium chloride (LiCl) solution in each session. An intestinal taste cue was mixed directly into the LiCl infusate for aversion training. Results showed that rats failed to detect intestinal sweet taste alone (20 mM Sucralose) but clearly suppressed licking in response to a nutritive sweet taste stimulus (234 mM sucrose) in the intestine that had been repeatedly paired with LiCl. Rats trained with ID sucrose in LiCl subsequently generalized responding to ID Sucralose alone at test. Replicating this, rats trained with ID Sucralose in compound with 80 mM Polycose rapidly suppressed licking to the 20 mM Sucralose alone in a later test. Furthermore, ID sweet taste signaling did not support the rapid negative feedback of sucrose or Polycose on intake when their digestion and transport were blocked. Together, these results suggest that other signaling pathways and/or transporters engaged by caloric carbohydrate stimuli potentiate detection of sweet taste signals in the intestine.     

The selective serotonin reuptake inhibitor paroxetine does not alter consummatory concentration-dependent licking of prototypical taste stimuli by rats

Serotonin and the 5HT(1A) receptor are expressed in a subset of taste receptor cells, and the 5HT(3) receptor is expressed on afferent fibers innervating taste buds. Exogenous administration of the selective serotonin reuptake inhibitor, paroxetine, has been shown to increase taste sensitivity to stimuli described by humans as sweet and bitter. Serotonergic agonists also decrease food and fluid intake, and it is possible that modulations of serotonin may alter taste-based hedonic responsiveness; alternatively, or in combination, serotonin may interact with physiological state to impact ingestive behavior. In this study, the unconditioned licking of prototypical taste stimuli by rats in brief-access taste tests was assessed following paroxetine administration (0.3-10 mg/kg intraperitoneal). We also measured sucrose licking by rats in different deprivation states after paroxetine (5 mg/kg). In neither experiment did we find any evidence of an effect of paroxetine on licking relative to water to any of the taste stimuli in the brief-access test at doses that decreased food intake. However, in some conditions, paroxetine decreased trials initiated to tastants. Therefore, a systemic increase in serotonin via paroxetine administration can decrease appetitive behavior in brief-access tests but is insufficient to alter taste-guided consummatory behavior.     

Greater superficial petrosal nerve transection in rats does not change unconditioned licking responses to putatively sweet taste stimuli

The greater superficial petrosal nerve (GSP), innervating taste buds in the palate, is known to be exceptionally responsive to sucrose, especially compared with the responsiveness of the chorda tympani nerve (CT). However, whereas transection of the CT (CTX) alone has little or no effect on unconditioned licking responses to many "sweet" stimuli, the impact of GSP transection (GSPX) alone is equivocal. To further examine the role of the GSP on licking responses to putatively sweet-tasting substances, brief-access taste tests were conducted in nondeprived rats before and after sham surgery (SHAM) or CTX or GSPX. A range of concentrations of sucrose, L-alanine, glycine, and L-serine, with and without 1.0 mM inosine monophosphate (IMP) added, were used. All groups showed significant concentration-dependent increases in licking to all stimuli presurgically and postsurgically. CTX decreased licking responses relative to SHAM rats in the first sucrose test. There was also a group x concentration interaction for L-alanine, but post hoc tests did not reveal its basis. Other than this, there were no significant differences among the surgical groups. Interestingly, rats with GSPX tended to initiate fewer trials than SHAM rats. Overall, after GSPX, the remaining gustatory nerves are apparently sufficient to maintain concentration-dependent licking responses to all stimuli tested here. The disparity between our results and others in the literature where GSPX reduced licking responses to sucrose is possibly related to differences in surgical technique or test trial duration.     

Effects of melanin-concentrating hormone on licking microstructure and brief-access taste responses

The effects of intracerebroventricular application of melanin-concentrating hormone (MCH) on licking for sucrose, quinine hydrochloride (QHCl), and water solutions were evaluated in two experiments. In experiment 1, rats received 90-min access to sucrose and water solutions after MCH or vehicle microinjection to the third ventricle (3V). MCH increased intake largely through increases in the rate of licking early in the meal and in the mean duration of lick bursts, suggesting an effect on gustatory evaluation. Therefore, in experiment 2, brief access tests were used with a series of sucrose and QHCl concentrations to behaviorally isolate the effects of intracerebroventricular MCH on gustatory evaluation. MCH uniformly increased licking for all sucrose solutions, water, and weak concentrations of QHCl; however, it had no effect on licking for the strongest concentrations of QHCl, which were generally avoided under control conditions. Thus MCH did not produce nonspecific increases in oromotor activity, nor did it change the perceived intensity of the tastants. We conclude that MCH enhanced the gain of responses to normally accepted stimuli at a phase of processing after initial gustatory detection and after the decision to accept or reject the taste stimulus. A comparison of 3V NPY and MCH effects on licking microstructure indicated that these two peptides increased intake via dichotomous behavioral processes; although NPY suppressed measures associated with inhibitory feedback from the gut, MCH appeared instead to enhance measures associated with hedonic taste evaluation.     

Multiple processes underlie benzodiazepine-mediated increases in the consumption of accepted and avoided stimuli

Hyperphagia is a reported side effect of anxiolytic benzodiazepines such as chlordiazepoxide (CDP). Prior research has focused primarily on the ingestive responses to sweet or solid foods. We examined CDP effects on licking for normally accepted and avoided taste solutions across a range of concentrations. The effect of CDP (10 mg/kg) versus saline on the licking patterns of water-restricted rats for water and 3 concentrations of sucrose, saccharin, NaCl, monosodium glutamate (MSG), citric acid, and quinine (Q-HCl) solutions was evaluated during 1 h tests. CDP increased meal size for all tastants except citric acid. Analysis of licking microstructure revealed 3 dissociable effects of CDP. CDP affected oromotor coordination as indicated by a uniform increase in the modal interlick interval for all stimuli. CDP increased meal size as indicated by shorter pauses during consumption of water, MSG, and weaker saccharin concentrations, and by fewer long interlick intervals (250-2000 ms) for normally avoided tastants. CDP also increased meal size by increasing burst size, burst duration, and the initial rate of licking for most solutions, suggesting increased hedonic taste evaluation. CDP did not affect variables associated with postingestive feedback such as meal duration or number of bursts, and the results also suggest that CDP did not enhance the perceived taste intensity. We hypothesize that the reduction of pause duration is consistent with an increased motivation to sample the stimulus that synergizes with changes in taste-mediated responsiveness to some but not all stimuli to yield increases in the consumption of both normally accepted and avoided taste stimuli.     

Duration, response, and location: the influence of upcoming 32% sucrose on rats' licking or lever pressing for 1% liquid sucrose

The present study investigated whether rats' rates of licking or pressing a lever for 1% liquid sucrose delivered by a continuous reinforcement schedule would decrease (contrast) or increase (induction) when the upcoming period would allow access to 32% sucrose and whether such changes would be influenced by how long each substance was available. In Experiment 1, different groups of rats licked a spout or pressed a lever for 1% sucrose in the first half of the session and, in different conditions, for 1% or 32% sucrose in the second half. Across conditions, halves of the session were 3, 6, 12, or 24 min long. Upcoming 32% sucrose significantly decreased rates of licking at each duration whereas it increased rates of lever pressing except when access duration was 3 min. Experiment 2 replicated Experiment 1 with the exception that rats that licked did so from the same spout in both halves of the session and rats that pressed a lever collected the sucrose reinforcers in the different halves at different locations. In these procedures, upcoming 32% sucrose significantly increased rates of licking. Significant, but small, increases in rates of lever pressing were still observed. The present results suggest that continuous reinforcement or duration of access to sucrose are not primary determinants of whether contrast or induction is observed. Rather, they suggest that the type of behavior (licking versus pressing a lever) and the location at which the substances are collected and consumed play a large role in which effect occurs.     

Extensive Gustatory Cortex Lesions Significantly Impair Taste Sensitivity to KCl and Quinine but Not to Sucrose in Rats

Recently, we reported that large bilateral gustatory cortex (GC) lesions significantly impair taste sensitivity to salts in rats. Here we extended the tastants examined to include sucrose and quinine in rats with ibotenic acid-induced lesions in GC (GCX) and in sham-operated controls (SHAM). Presurgically, immediately after drinking NaCl, rats received a LiCl or saline injection (i.p.), but postsurgical tests indicated a weak conditioned taste aversion (CTA) even in controls. The rats were then trained and tested in gustometers to discriminate a tastant from water in a two-response operant taste detection task. Psychometric functions were derived for sucrose, KCl, and quinine. Our mapping system was used to determine placement, size, and symmetry of the lesions (~91% GC damage on average). For KCl, there was a significant rightward shift (ΔEC₅₀ = 0.57 log₁₀ units; p<0.001) in the GCX psychometric function relative to SHAM, replicating our prior work. There was also a significant lesion-induced impairment (ΔEC₅₀ = 0.41 log₁₀ units; p = 0.006) in quinine sensitivity. Surprisingly, taste sensitivity to sucrose was unaffected by the extensive lesions and was comparable between GCX and SHAM rats. The fact that such large bilateral GC lesions did not shift sucrose psychometric functions relative to SHAM, but did significantly compromise quinine and KCl sensitivity suggests that the neural circuits responsible for the detection of specific taste stimuli are partially dissociable. Lesion-induced impairments were observed in expression of a postsurgical CTA to a maltodextrin solution as assessed in a taste-oriented brief-access test, but were not reflected in a longer term 46-h two-bottle test. Thus, deficits observed in rats after extensive damage to the GC are also dependent on the test used to assess taste function. In conclusion, the degree to which the GC is necessary for the maintenance of normal taste detectability apparently depends on the chemical and/or perceptual features of the stimulus.     

Water restriction and fluid temperature alter preference for water and sucrose solutions

The role of diet temperature in ingestive behavior is poorly understood. We examined the importance of stimulus temperature and water-restriction state on the preference for and intake of water and sucrose. Using custom-designed equipment that allows us to monitor and maintain solution temperatures during testing (±0.1 °C), we conducted a series of 2-bottle preference tests (10 °C water vs. sucrose 10-40 °C) and brief access tests (10-40 °C water and sucrose). Water-restricted rats preferred cold water over any sucrose concentration (0.0-1.0 M) if the sucrose was 30 or 40 °C, whereas the same rats preferred sucrose at all concentrations and temperatures when unrestricted suggesting that the water-restriction state interacts with temperature preference. In a series of brief-access tests using a Davis Rig (MS-180), rats reduced licking to cold sucrose compared with 20 °C sucrose, suggesting that unlike water, cold temperature reduced the palatability of sucrose.     

Comparison of anorectic drugs in rats trained to discriminate between satiation and deprivation

Eight male rats were trained to discriminate between the internal states produced by food deprivation of 3 hours (satiation) and that produced by food deprivation of 27 hours duration (deprivation). One lever, in a two-lever operant chamber, had to be pressed to receive reinforcement in the satiation state, whereas pressing the other lever was required when the rat was in the deprivation state. Once the rats were trained, increasing the number of hours of food deprivation, from 1 to 48 hours, resulted in more deprivation-appropriate lever responses in the two-lever operant task. Administration of doses of fenfluramine (0.5-1.5 mg.kg), its active metabolite norfenfluramine (0.25-1.0 mg/kg) or d-amphetamine (0.5-1.5 mg/kg) produced a dose-responsive decrease in deprivation-appropriate responses when each drug/dose was injected (i.p.) 15 min prior to deprivation (27 hours) testing. Norfenfluramine was 1.5 times more potent than fenfluramine which was 1.5 times more potent than amphetamine.     

Anatomical dissociation of melanocortin receptor agonist effects on taste- and gut-sensitive feeding processes

Injections of the melanocortin 3/4 receptor (MCR) agonist melanotan II (MTII) to a variety of brain structures produces anorexia, suggesting distributed brain MCR control of food intake. We performed a detailed analysis of feeding behavior (licking microstructure analysis) after a range of MTII doses (0.005 nM to 1 nM) was targeted to the forebrain (third ventricle, 3V) or hindbrain (fourth ventricle, 4V) regions. MTII (0.1 nM and 1 nM) delivered to the 3V or 4V significantly reduced 0.8 M sucrose intake. The anorexia was mediated by reductions in the number of licking bursts in the meal, intrameal ingestion rate, and meal duration; these measures have been associated with postingestive feedback inhibition of feeding. Anorexia after 3V but not 4V MTII injection was also associated with a reduced rate of licking in the first minute (initial lick rate) and reduced mean duration of licking bursts; these measures have been associated with taste evaluation. MTII effects on taste evaluation were further explored: In experiment 2, 3V MTII (1 nM) significantly reduced intake of noncaloric 4 mM saccharin and 0.1 M and 1 M sucrose solutions, but not water. The anorexia was again associated with reduced number of licking bursts, ingestion rate, meal duration, initial lick rate, and mean burst duration. In experiments 3 and 4, brief access (20 s) licking responses for sweet sucrose (0.015 M to 0.25 M) and bitter quinine hydrochloride (0.01 mM to 1 mM) solutions were evaluated. Licking responses for sucrose were suppressed, whereas those for quinine solutions were increased after 3V MTII, but not after 4V MTII injections (0.1 nM and 1 nM). The results suggest that multiple brain MCR sites influence sensitivity to visceral feedback, whereas forebrain MCR stimulation is necessary to influence taste responsiveness, possibly through attenuation of the perceived intensity of taste stimuli.     

Instrumental responding remains under the control of the consequent outcome after extended training

The effect of extensive training on the contribution of response--outcome learning to instrumental performance in rats was re-examined in two experiments using a transfer test. In each experiment, two discriminative stimuli were established as signals for different response--outcome combinations (e.g. light: nose poke-pellets and noise: handle pull-sucrose). Then, two different responses (lever press and chain pull) were concurrently trained with those outcomes. In Experiment 1, these responses underwent extensive training, each with a different outcome (e.g. lever press-pellets and chain pull-sucrose). In Experiment 2, these responses were trained moderately with one outcome (e.g. lever press-pellets and chain pull-sucrose) and extensively with a different outcome (e.g. lever press-sucrose and chain pull-pellets). Finally, transfer tests were conducted in which the discriminative stimuli, noise and light, were tested periodically with the lever and chain. In Experiment 1, the stimuli consistently and preferentially elevated performance of the response trained with the same outcome relative to that trained with a different outcome. In Experiment 2, the stimuli elevated both responses nondifferentially. However, a drive manipulation (thirst) designed to increase the value of sucrose relative to pellets revealed a significant preference for the response that had been extensively trained with sucrose. Overall, the results of these experiments confirm previous findings that instrumental behaviors do not become increasingly independent of their consequent outcomes with extended training. However, the transfer results of Experiment 2 highlight a potential limitation of the transfer test for assessing variations in the strength of R--O associations.     

Passive immunization against nicotine attenuates nicotine discrimination

Ten rats were trained in a two lever operant chamber to press different levers after a nicotine injection (0.14 mg/kg s.c.) or a saline injection on an FR10 schedule. The rats were then injected i.p. with either 150 mg nicotine-specific IgG or the same amount of control IgG from non-immunized rabbits. On successive days, they were retested with both levers active after a saline injection, a full training dose of nicotine and a half dose of nicotine (0.07 mg/kg s.c.). After saline injection, both groups pressed the saline lever almost exclusively. After each of the nicotine doses, the immunized rats performed a significantly lower percentage of their lever presses on the nicotine lever than did non-immunized rats. The results suggest that passive immunization can interfere with the stimulus properties of nicotine.     

Linoleic and oleic acids alter the licking responses to sweet, salt, sour, and bitter tastants in rats

The free fatty acids (FFAs), linoleic and oleic acids, commonly found in dietary fats can be detected by rats on the basis of gustatory cues following conditioned taste aversion pairings. FFAs depolarize the membrane potential of isolated rat taste receptor cells by inhibiting delayed rectifying potassium channels. This study examined the licking response of rats to sweet, salt, sour, and bitter taste solutions when 88 muM linoleic acid, 88 muM oleic acid, or an 88 muM linoleic-oleic acid mixture was added to the solutions. The presence of linoleic, oleic, and the linoleic-oleic acid mixture in sweet solutions produced increases in the licking responses, whereas adding linoleic, oleic, and the linoleic-oleic acid mixture to salt, sour, or bitter taste solutions produced decreases in licking responses when compared with the licking responses to the solutions in the absence of the FFAs. We conclude that FFAs may act in the oral cavity to depolarize taste receptor cells and therefore to increase the perceived intensity of concomitant tastants, thus contributing to the enhanced palatability associated with foods containing high dietary fat.     

Citric acid and quinine share perceived chemosensory features making oral discrimination difficult in C57BL/6J mice

Evidence in the literature shows that in rodents, some taste-responsive neurons respond to both quinine and acid stimuli. Also, under certain circumstances, rodents display some degree of difficulty in discriminating quinine and acid stimuli. Here, C57BL/6J mice were trained and tested in a 2-response operant discrimination task. Mice had severe difficulty discriminating citric acid from quinine and 6-n-propylthiouracil (PROP) with performance slightly, but significantly, above chance. In contrast, mice were able to competently discriminate sucrose from citric acid, NaCl, quinine, and PROP. In another experiment, mice that were conditioned to avoid quinine by pairings with LiCl injections subsequently suppressed licking responses to quinine and citric acid but not to NaCl or sucrose in a brief-access test, relative to NaCl-injected control animals. However, mice that were conditioned to avoid citric acid did not display cross-generalization to quinine. These mice significantly suppressed licking only to citric acid, and to a much lesser extent NaCl, compared with controls. Collectively, the findings from these experiments suggest that in mice, citric acid and quinine share chemosensory features making discrimination difficult but are not perceptually identical.     

The sweet-bitter taste of alcohol: aversion generalization to various sweet-quinine mixtures in the rat

Rats were trained to avoid a 5% alcohol solution and then testedwith either sweet + quinine hydrochloride solutions (Experiment1) or sweet + hydrochloric acid solutions (Experiment 2). Thesweet stimuli used were sucrose, glucose, fructose and saccharin.Significant aversion generalization was found only in Experiment1 where trained rats generalized to all four test stimuli, thussuggesting that alcohol has a sweet taste (in combination withbitter) not specific to one sweetener. No significant aversiongeneralization was noted in Experiment 2 when sweet + hydrochloricacid solutions were tested. In Experiment 3, rats were trainedto avoid 6% alcohol and tested with sucrose + quinine hydrochloridemixtures with varying concentrations of each component. In general,rats showed generalization of the alcohol aversions across thevarious concentrations of sucrose and quinine hydrochloridetested.     

Sham feeding corn oil increases accumbens dopamine in the rat

Both real and sham feeding of sucrose increase dopamine (DA) overflow in the nucleus accumbens (NAc). Fat is another constituent of foods that is inherently preferred by humans and rodents. We examined the affect of sham feeding corn oil in rats that were food and water deprived overnight. Rats were implanted with guide cannulas aimed at the NAc, as well as gastric fistulas. On alternate days, they were trained to sham lick 100% corn oil or distilled water (dH2O) for 20 min in the morning. Twenty-minute microdialysis samples were taken before, during, and after sham licking. DA and monoamines were analyzed by reverse-phase HPLC with coulometric detection. The results show that DA release in the NAc was significantly increased during sham licking of corn oil compared with the prior baseline (157.5+/-18.8%, n=12). During sham licking of dH2O, DA release in the NAc was not changed (93.0+/-4.0%, n=15). This experiment demonstrates that sham feeding of corn oil releases accumbens DA in a manner similar to ingestion of sucrose. Although both stimuli may have an olfactory component, sucrose is a gustatory, and 100% corn oil appears to be a trigeminal stimulus. Thus these data support the hypothesis that different sensory modalities produce reward using the same or closely related substrates in the forebrain.     

The relative affective potency of glycine, L-serine and sucrose as assessed by a brief-access taste test in inbred strains of mice

In general, rodents prefer both sucrose and L-serine relative to water and treat both compounds as possessing a similar taste quality (e.g. 'sweetness') despite that they are believed to bind with different T1R heterodimeric receptors in taste bud cells. We assessed the affective potency of these compounds along with glycine, which is thought to bind with both T1R receptor complexes, using a brief-access taste test in a gustometer. Unconditioned licking responses of two 'taster' strains (C57BL/6J and SWR/J), which display high preference for low concentrations of sucrose, and two 'non-taster' (129P3/J and DBA/2J) strains, which display blunted preference for low concentrations of sucrose, were measured during 5 s trials of varying concentrations of a single compound when mice (n=10/strain/stimulus) were non-deprived and when access to home-cage water was restricted. In non-deprived mice, sucrose generated monotonically increasing concentration-response curves regardless of strain, whereas glycine was only marginally effective at stimulating licking and L-serine produced relatively flat functions. The profile of responsiveness across strains was more complex than expected. For example, when tested with sucrose in the non-deprived condition, the 129P3/J non-taster strain surpassed the responsiveness of taster mice at mid-range to high concentrations. Under water-restricted conditions, these mice also were significantly more responsive to high concentrations of both sucrose and glycine compared with the other strains when stimulus licking was standardized relative to water. Thus, the affective potency of the stimuli tested here seems to be related to the ability of the compounds to bind with the T1R2+3 receptor complex. However, the profile of strain responsiveness to these tastants in the brief-access test does not appear to be simply explained by the sweetener 'taster' status of the strain.     

The taste of polycose in hamsters

Hamsters show a preference for Polycose, a mixture of starch-derived glucose polymers, that is as strong as their preference for sucrose. However, in the hamster, taste aversions to Polycose may be less easily acquired than taste aversions to sucrose and the qualitative aspects of Polycose are unknown in this species. In order to examine the taste of Polycose in the hamster, we utilized a taste-aversion protocol with two conditioning trials. Animals were trained to avoid one of three different conditioning stimuli: 50 mM sucrose, 100 mM Polycose and a mixture of 50 mM sucrose with 100 mM Polycose. Control animals were conditioned with deionized water. After the second conditioning trial, generalization testing began for the three conditioning stimuli plus 3 mM citric acid, 300 mM KCI and 30 mM NaCl. The results showed that aversions to Polycose, sucrose or the Polycose/sucrose mixture cross- generalized, demonstrating that Polycose and sucrose share a common taste percept in the hamster. None of the aversions generalized to NaCl, citric acid or KCI. In addition, comparisons among the patterns of taste generalizations indicated that the tastes of Polycose and sucrose also had distinct qualitative components. Finally, although the taste of 100 mM Polycose was more salient than the taste of 50 mM sucrose, the taste of sucrose could still be detected in a mixture with Polycose.      

Quantifying Social Motivation in Mice Using Operant Conditioning

In this protocol, social motivation is measured in mice through a pair of operant conditioning paradigms. To conduct the experiments, two-chambered shuttle boxes were equipped with two operant levers (left and right) and a food receptacle in one chamber, which was then divided from the second chamber by an automated guillotine door covered by a wire grid. Different stimulus mice, rotated across testing days, served as a social stimulus behind the wire grid, and were only visible following the opening of the guillotine door. Test mice were trained to lever press in order to open the door and gain access to the stimulus partner for 15 sec. The number of lever presses required to obtain the social reward progressively increased on a fixed schedule of 3. Testing sessions ended after test mice stopped lever pressing for 5 consecutive minutes. The last reinforced ratio or breakpoint can be used as a quantitative measure of social motivation. For the second paradigm, test mice were trained to discriminate between left and right lever presses in order to obtain either a food reward or the social reward. Mice were rewarded for every 3 presses of each respective lever. The number of food and social rewards can be compared as a measurement of the value placed upon each reward. The ratio of each reward type can also be compared between mouse strains and the change in this ratio can be monitored within testing sessions to measure satiation with a given reward type. Both of these operant conditioning paradigms are highly useful for the quantification of social motivation in mouse models of autism and other disorders of social behavior.