Stimulus specificity in the acquisition and extinction of conditioned taste aversion

An experiment evaluated whether the acquisition and extinction of conditioned taste aversion in the rat is stimulus-specific by testing the degree of response transfer between sweet and salty tastes. Animals in the paired-same and paired-different groups received a presentation of a gustatory CS and a cyclophosphamide injection US. Nonconditioned control groups received unpaired CS /US presentations or the CS followed by a vehicle injection. Taste avoidance was evaluated in three nonreinforced test sessions. In the paired-same, unpaired and vehicle groups, all test sessions were conducted with the same flavor as originally used in training, whereas the paired-different group was tested with a novel flavor on the first and second sessions and with the originally trained flavor in last session. Stimulus specific acquisition was apparent in the first test session, when the animals in the group paired-same exhibited lower fluid intake than the other three groups. Evidence of specificity of extinction was apparent in the last test session, when animals in the group paired-different exhibited lower fluid intake than the other three groups. These results provide further evidence of stimulus specificity in acquisition and extinction of conditioned taste aversion, supporting the associative interpretation of these phenomena.     

Gamma-L-glutamyl-taurine (Litoralon) affects conditioned taste aversion in rats

The dipeptide gamma-L-glutamyl-taurine (Litoralon) reduced neophobia of rats at a dose of 5.0 mg/kg (i.p.) in a "one-bottle forced choice paradigm" for conditioned taste aversion (CTA), but did not significantly affect the rats' "memory" of intoxication following chronic treatment at doses of 0.05, 0.50 and 5.00 mg/kg (i.p.). Acute treatment with Litoralon (10-1000 micrograms/kg, i.p.) did not affect CTA checked in a "two-bottle test", when administered immediately following the unconditioned stimulus (LiCl injection). In contrast, when given 90 min prior to the retention test, the injection of Litoralon (50.0 micrograms/kg) and gamma-aminobutyryl ethanolamine phosphate (100 and 500 micrograms/kg) resulted in a significantly higher intake of saccharin solution by the rats. This effect is comparable to the action of diazepam tested in the same experimental procedure. The results support our hypothesis about the anti-conflict potencies of these dipeptides, exerted by reducing aversion of phobia and/or the anxiety level of the animals in the experimental situation.     

Attenuation of a radiation-induced conditioned taste aversion after the development of ethanol tolerance

An attempt to reduce a radiation-induced conditioned taste aversion (CTA) was undertaken by rendering animals tolerant to ethanol. Ethanol tolerance, developed over 5 days, was sufficient to block a radiation-induced taste aversion, as well as an ethanol-induced CTA. Several intermittent doses of ethanol, which did not induce tolerance but removed the novelty of the conditioning stimulus, blocked an ethanol-induced CTA but not the radiation-induced CTA. A CTA induced by doses of radiation up to 500 rads was attenuated. These data suggest that radioprotection developing in association with ethanol tolerance is a result of a physiological response to the chronic presence of ethanol not to the ethanol itself.     

Brain regions responsible for the expression of conditioned taste aversion in rats

Conditioned taste aversion (CTA) is acquired when the ingestion of a food is followed by malaise. CTA is a kind of fear learning making animals avoid subsequent intake of the food and show aversive behavior to the taste of the food. To elucidate the brain regions responsible for the expression of CTA, our previous electrophysiological and recent c-fos immunohistochemical studies have been reviewed. Among a variety of brain regions including the parabrachial nucleus, amygdala, insular cortex, supramammillary nucleus, nucleus accumbens, and ventral pallidum that are involved in different phases of CTA expression, the enhanced taste sensitivity to facilitate detection of the conditioned stimulus may originate in the central nucleus of the amygdala and the hedonic shift, from positive to negative, may originate in the basolateral nucleus of the amygdala.     

咸味觉厌恶模型大鼠鼓索神经对味觉刺激的电生理反应特性

目的:探索大鼠咸味觉厌恶建立后外周鼓索神经(CT)对咸味觉及其他味觉刺激的电生理反应特性的改变。方法:将14只SD成年雄性大鼠分为咸味觉厌恶模型组(CTA)和对照组(n=7/group)。实验第1日给予大鼠30min的0.1mol/LNaCl饮食,随后CTA组和对照组大鼠分别腹腔注射2ml0.15mol/LLiCl和同等量生理盐水。在第2、3和4日,测量两组大鼠每天30min内对NaCl和蒸馏水饮用量。于第4日行为学测试后,分别记录CTA组大鼠和对照组大鼠CT对口内给予系列浓度NaCl溶液、0.3mol/LNaCl与0.1mmol/L阿米洛利(一种舌上皮钠通道阻断剂)混合液和其他四种基本味觉刺激溶液的电生理反应。结果:与对照组相比,CTA组大鼠CT对系列浓度NaCl和其他4种基本味觉刺激的电生理反应特性没有发生明显变化(P>0.05);舌上皮钠通道阻断剂阿米洛利强烈抑制CTA大鼠对NaCl的反应(P<0.01)。结论:条件性咸味觉厌恶模型大鼠CT对各种味觉刺激的电生理反应特性没有发生明显改变。     

Blocking of acquisition of a taste aversion by a context experienced prior to the taste

This experiment tested the proposal that events taking place before a rat has access to a taste can proactively interfere with acquisition of an aversion to the taste when this has been followed by lithium chloride injection. Rats were initially given context discrimination whereby placement in one distinctive context (target) was followed by lithium injection, while placement in a second context (safe) was followed by saline injection. In the subsequent 1-trial taste conditioning session, rats were first placed in either their target context (Blocking group), their safe context (Control-Safe group) or a neutral context (Control-Neutral group), then given access to sucrose and 30 min later were injected with lithium. Subsequent tests of sucrose intakes revealed a blocking effect. These results indicate that proactive interference with taste aversion learning by a context can occur that is unlikely to be based on generalization decrement.     

Some critical factors involved in formation of conditioned taste aversion to sodium chloride in rats

Some factors concerning acquisition and retention of conditionedtaste aversions (CTAs) were behaviorally examined in the rat.In the CTA paradigm, aqueous solution of 0.1 M NaCl was usedas the conditioned stimulus (CS) and an intraperitoneal (i.p.)injection of 0.15 M LiCl was employed as the unconditioned stimulus(US). In experiment 1, CTAs to 0.1 M NaCl were examined in bothforward (CS–US) and backward (US–CS) conditioningparadigms. Reliable CTAs were produced in the US–CS conditioningparadigm when the US–CS interval was less than 10 min,as well as in the CS–US conditioning paradigm. In experiment2, strong CTAs to 0.1 M NaCl were established when water-deprivedrats made at least 500 continuous licks, corresponding to 2.5ml intake and 2 min of drinking time. In experiment 3, effectsof gustatory deafferentation on CTA formation were studied.Only the chorda tympani played an important role in acquisitionand retention of CTAs to NaCl solutions. These results ipHimMthat strong CTAs can be acquired to 0.1 M NaCl, if its tasteinformation which is conveyed via the chorda tympani duringthe 500 continuous licks is followed by LiCl-induced sickness.     

Opioids affect acquisition of LiCl-induced conditioned taste aversion: involvement of OT and VP systems

Aversive properties of lithium chloride (LiCl) are mediated via pathways comprising neurons of the nucleus of the solitary tract (NTS) and oxytocin (OT) and vasopressin (VP) cells in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei. Because opioids act on brain regions that mediate effects of LiCl, we evaluated whether administration of opioids shortly before LiCl in rats influences 1) development of conditioned taste aversion (CTA) and 2) activation of NTS neurons and OT/VP cells. Neuronal activation was assessed by applying c-Fos immunohistochemical staining. Three opioids were used: morphine (MOR), a mu-agonist, butorphanol tartrate (BT), a mixed mu/kappa-agonist, and nociceptin/orphanin FQ (N/OFQ), which binds to an ORL1 receptor. BT and N/OFQ completely blocked acquisition of CTA. MOR alleviated but did not eliminate the aversive effects. Each of the opioids decreased LiCl-induced activation of NTS neurons as well as OT and VP cells in the PVN and SON. We conclude that opioids antagonize aversive properties of LiCl, presumably by suppressing activation of pathways that encompass OT and VP cells and NTS neurons.     

Monosodium glutamate and sweet taste: generalization of conditioned taste aversion between glutamate and sweet stimuli in rats

Even though monosodium glutamate (MSG) is a prototypical umami substance, previous studies reported that a conditioned taste aversion (CTA) to MSG, mixed with amiloride to block the taste of sodium, generalizes to sucrose. These findings suggest that the taste of glutamate mimics the taste of sucrose and raise the question of whether glutamate has a broadly tuned sweet taste component. To test this hypothesis, CTA experiments were conducted to test for generalization between MSG and several sweet stimuli: sucrose, glucose, maltose, saccharin and SC-45647. Strong bidirectional generalization was seen between MSG mixed with amiloride and sucrose, glucose, saccharin and SC-45647. Weak generalization was seen between MSG and maltose, and sucrose and maltose. None of the CTAs generalized to NMDA. These findings support the hypothesis that the taste of MSG has broadly tuned, sweet-like characteristics, possibly due to the convergence of afferent signals for MSG, natural sugars and artificial sweeteners.     

Dose-dependent effects of peptide YY(3-36) on conditioned taste aversion in rats

We used a conditioned taste aversion test to assess whether PYY(3-36) reduces food intake by producing malaise. Two-hour IV infusion of PYY(3-36) (8, 15, and 30 pmol/kg/min) at dark onset in non-food-deprived rats produced a dose-dependent inhibition of feeding and a conditioned aversion to the flavored chow paired with PYY(3-36) infusion. In food-deprived rats, PYY(3-36) at 2 and 4 pmol/kg/min inhibited intake of a flavored saccharin solution without producing conditioned taste aversion, whereas higher doses (8 and 15 pmol/kg/min) inhibited saccharin intake and produced taste aversion. These results suggest that anorexic doses of PYY(3-36) may produce a dose-dependent malaise in rats, which is similar to that reported for PYY(3-36) infusion in humans. Previous studies have shown that PYY(3-36) potently inhibits gastric emptying, and that gut distention can produce a conditioned taste aversion. Thus, PYY(3-36) may produce conditioned taste aversion in part by slowing gastric emptying.     

Estradiol benzoate can function as an unconditioned stimulus in a conditioned taste aversion paradigm

The extent to which gonadal steroid hormones can serve as unconditioned stimuli in a conditioned taste aversion paradigm was examined in Rockland-Swiss albino mice. With saccharin serving as the conditioned stimulus, subcutaneously injected estradiol benzoate, but not progesterone or testosterone propionate, was found to be a potent unconditioned stimulus in both male and female mice. Dose-response effects were also observed; increasing dosages of estradiol benzoate led to increasingly stronger conditioned aversions in both males and females. The aversion detected in males was more resistant to extinction than that seen in females. Prepubertal gonadectomy reversed the sex-dependent effects of estradiol benzoate in learned aversions in adulthood; castration of males promoted the extinction process, whereas ovariectomy of females retarded extinction. The results may be useful for our understanding of the mechanisms involved in conditioned taste aversion learning as well as a wide array of hormone-dependent behavioral responses.     

Electrophysiological analysis of retrieval of conditioned taste aversion in rats. Unit activity changes in critical brain regions.

Gustatory discrimination testing shows that rats with an overtrained conditioned taste aversion (CTA) to isotonic LiCl stop salt intake after 1 to 2 licks at the LiCl spout and move to the adjacent water spout within 0.7 s. Activity of 526 neurones from the nucleus of the solitary tract, gustatory thalamus, gustatory cortex, lateral and ventromedial thalamus, and amygdala was recorded in naive or CTA trained rats during the above gustatory discrimination. Post-stimulus histograms (PSH) triggered by water or salt licks or by spout switching were plotted for single units. Population responses of various regions were obtained by integration of the statistically significant excitatory and inhibitory intervals in the individual PSHs. Lick related changes of unit activity were orserved in 52% and 65% of neurones in control and CTA trained rats, respectively. The CTA training increased the incidence of units in which salt licking influenced the activity less than water licking. Presentation of the aversive fluid induced inhibition of unit activity in the gustatory cortex, ventromedial hypothalamus, and amygdala and excitation in the lateral hypothalamus. The changes started 100 to 150 ms after spout switching and culminated 100 ms later. Activity of the solitary tract nucleus and gustatory thalamus was affected less consistently. The results indicate that the gustatory cortex, amygdala and hypothalamus participate in CTA retrieval but a more specific identification of the electrical correlates of memory readout and of drinking control was not possible.     

Effects of exogenous cholecystokinin octapeptide on acquisition of naloxone precipitated withdrawal induced conditioned place aversion in rats

Cholecystokinin octapeptide (CCK-8), a gut-brain peptide, regulates a variety of physiological behavioral processes. Previously, we reported that exogenous CCK-8 attenuated morphine-induced conditioned place preference, but the possible effects of CCK-8 on aversively motivated drug seeking remained unclear. To investigate the effects of endogenous and exogenous CCK on negative components of morphine withdrawal, we evaluated the effects of CCK receptor antagonists and CCK-8 on the naloxone-precipitated withdrawal-induced conditioned place aversion (CPA). The results showed that CCK2 receptor antagonist (LY-288,513, 10 μg, i.c.v.), but not CCK1 receptor antagonist (L-364,718, 10 μg, i.c.v.), inhibited the acquisition of CPA when given prior to naloxone (0.3 mg/kg) administration in morphine-dependent rats. Similarly, CCK-8 (0.1-1 μg, i.c.v.) significantly attenuated naloxone-precipitated withdrawal-induced CPA, and this inhibitory function was blocked by co-injection with L-364,718. Microinjection of L-364,718, LY-288,513 or CCK-8 to saline pretreated rats produced neither a conditioned preference nor aversion, and the induction of CPA by CCK-8 itself after morphine pretreatments was not significant. Our study identifies a different role of CCK1 and CCK2 receptors in negative affective components of morphine abstinence and an inhibitory effect of exogenous CCK-8 on naloxone-precipitated withdrawal-induced CPA via CCK1 receptor.     

Tests of adipsia and conditioned taste aversion following the intrahypothalamic injection of amylin.

Intrahypothalamic injection of amylin (AMY) was shown to reduce the intake of rat chow and water for 8 and 4 h, respectively, in schedule-fed rats. Amylin also reduced water intake to a much lesser degree in 24-h water-deprived rats. A test of the ability of AMY to form a conditioned taste aversion yielded no change in saccharin preference, as compared to controls treated with vehicle. These results suggest that although AMY has adipsic effects, the reduction in water is not of sufficient magnitude to cause the anorexia. In addition, the failure of AMY to support a conditioned taste aversion suggests that AMY does not cause anorexia by inducing malaise. Therefore, in addition to other metabolic effects, AMY may be involved in the control of food and water intake.