Evaluation of rate-dependency and internal clock effects of D-amphetamine

The impact of two doses of d-amphetamine on rats' peak-interval performance was evaluated at two different points of training: with minimum training, 20 sessions, and with extended training, 120 sessions. At both points of training, none of the doses changed the location of the peak time; however, both doses caused a significant increase in the standard deviation of the response distribution during peak trials. Both results are incompatible with some previous empirical results, and with timing accounts that assume that dopamine modulates the pacemaker rate, but are compatible with a rate-dependent effect.     

Interval timing in rats: tracking unsignaled changes in the fixed interval schedule requirement

The present experiment examined interval timing in rats under dynamic conditions. A session began with FI60 s intervals, changed to a FI20 s, FI30 s, or FI40 s schedule at an unpredictable point, and then returned to a FI60 s schedule after the rats received 1, 8, or 24 successive short FI intervals. Variations in the duration and number of shorter intervals occurred across sessions and conditions. We observed rapid control of wait time duration by the FI duration of the preceding interval (one-back tracking), and changes in wait time depended on the number and duration of the shorter intervals. Furthermore, we observed proportional and scalar timing effects in overall wait time duration. The results provide information about the relation between interval timing under dynamic and steady state conditions.     

Mechanical responses of tendons to repeated extensions and wait periods

Tendon specimens were repeatedly extended to peak strains of either 2, 3, 4, or 6 percent. During the three 1800 s (30 min.) periods of cyclic extension, the peak loads relaxed with decreases in hysteresis and increases in slack strain. During the two 1800 s wait periods of no extension, the specimens recovered with increases in peak load and hysteresis and decreases in slack strain. However, the recovery during the wait periods was eradicated in the first few subsequent extensions and the relaxation continued as if there were no 1800 s wait periods. Stress-strain responses were well fit with power relations.     

The relevance of food peak architecture in trophic interactions

Phenological shifts and associated changes in the temporal match between trophic levels have been a major focus of the study of ecological consequences of climate change. Previously, the food peak has been thought to respond as an entity to warming temperatures. However, food peak architecture, that is, timings and abundances of prey species and the level of synchrony between them, determines the timing and shape of the food peak. We demonstrate this with a case example of three passerine prey species and their predator. We explored temporal trends in the timing, height, width, and peakedness of prey availabilities and explained their variation with food peak architecture and ambient temperatures of prebreeding and breeding seasons. We found a temporal match between the predator's breeding schedule and food availability. Temporal trends in the timing of the food peak or in the synchrony between the prey species were not found. However, the food peak has become wider and more peaked over time. With more peaked food availabilities, predator's breeding success will depend more on the temporal match between its breeding schedule and the food peak, ultimately affecting the timing of breeding in the predator population. The height and width of the food peak depended on the abundances and breeding season lengths of individual prey species and their reciprocal synchronies. Peakednesses of separate prey species' availability distributions alone explained the peakedness of the food peak. Timing and quantity of food production were associated with temperatures of various time periods with variable relevance in different prey species. Alternating abundances of early and late breeding prey species caused high annual fluctuation in the timing of the food peak. Interestingly, the food peak may become later even when prey species' schedules are advanced. Climate warming can thus produce unexpected changes in the food availabilities, intervening in trophic interactions.     

Acute effects of d-amphetamine on the differential reinforcement of low-rate (DRL) schedule behavior in the rat: comparison with selective dopamine receptor antagonists

Amphetamine and it analogs have been shown to affect operant behavior maintained on the differential reinforcement of a low-rate (DRL) schedule. The aim of the present study was to investigate what specific component of the DRL response is affected by d-amphetamine. The acute effects of d-amphetamine on a DRL task were compared with those of the selective dopamine D1 and D2 receptor antagonists, SCH23390 and raclopride, respectively. Pentylenetetrazole and ketamine were also used as two reference drugs for comparison with d-amphetamine as a psychostimulant. Rats were trained to press a lever for water reinforcement on a DRL 10-s schedule. Acute treatment of d-amphetamine (0, 0.5, and 1.0 mg/kg) significantly increased the response rate and decreased the reinforcement in a dose-related fashion. It also caused a horizontal leftward shift in the inter-response time (IRT) distribution at the doses tested. Such a shifting effect was confirmed by a significant decrease in the peak time, while the mean peak rate and burse response remained unaffected. In contrast, both SCH23390 (0, 0.05, and 0.10 mg/kg) and raclopride (0, 0.2, and 0.4 mg/kg) significantly decreased the total, non-reinforced, and burst responses. The de-burst IRT distributions were flattened out as shown by the dose-related decreases in the mean peak rate for both dopamine antagonists, but no dramatic shift in peak time was detected. Interestingly, neither pentylenetetrazole (0, 5, and 10 mg/kg) nor ketamine (0, 1, and 10 mg/kg) disrupted the DRL behavioral performance. It is then conceivable that d-amphetamine at the doses tested affects the temporal regulation of DRL behavior. The effectiveness of d-amphetamine is derived from its drug action as a psychostimulant. Taken together, these data suggest that different behavioral components of DRL task are differentially sensitive to pharmacological manipulation.     

Tolerance pattern to amphetamine anorexia after selective lesions in the hypothalamic dopaminergic projection

Tolerance to the anorexic effect of d-amphetamine was studied in rats with selective dopamine lesions in the forebrain by means of 6-hydroxy dopamine, and measuring the food intake during two consecutive 2 h periods. Lesions placed in the perifornical hypothalamus (PFH) strongly antagonised the anorexic effect, whereas, lesions produced via intraventricular injections affected the anorexia only marginally. Amphetamine anorexia observed in the first 2 h in control and lesioned groups remained persistently, without any evidence of tolerance, up to 2 weeks of treatment. The second 2 h food intake exhibited a progressive increase which contributed to the apparent tolerance seen in total 4 h food intake in the control and lesioned animals. The onset and completion of this apparent tolerance was markedly delayed in the dopamine depleted group; lesions placed in the relatively medial areas delayed the tolerance development more effectively than that of PFH lesions. The stimulant effect of amphetamine on locomotion was abolished in lesioned animals. The results indicate that an apparent tolerance to amphetamine anorexia still developed in animals with forebrain dopamine loss. Although both the beta adrenergic and dopaminergic systems act together in mediating AMPH anorexia, the onset and the rate of completion of tolerance appear to be under the influence of hypothalamic dopaminergic system.     

Reverse tolerance to amphetamine of mice bearing unilateral striatal lesions: effect upon the circling response to apomorphine

When mice bearing unilateral lesions of the striatum receive weekly doses of amphetamine, their circling responses increase with successive doses, i.e., they become reverse tolerant (1). The present work was undertaken to ascertain whether presynaptic dopaminergic changes might underlie this phenomenon. This was approached by observing whether the response to a direct dopaminergic agent would be affected by the development of reverse tolerance to amphetamine. The circling responses of unilaterally electrothermally lesioned mice to apomorphine, 0.4 mg/kg s.c., increased significantly after four weekly 4 mg/kg s.c. doses of d-amphetamine. The responses to apomorphine of mice not exposed to amphetamine declined over the same interval. The conclusion drawn is that presynaptic effects are not likely to underlie the phenomenon of reverse tolerance.     

D-amphetamine-induced hypothermia and hypermotility in rats: Changes after systemic administration of beta-endorphin

Systemically administered beta-endorphin was tested in rats for its ability to modify the hypothermia and hypermotility induced by d-amphetamine. Colonic temperature and motor activity were measured in a cold (4°C) ambient temperature in animals given IP injections of beta-endorphin (0.1, 1.0, or 3.0 mg/kg), naloxone (10 mg/kg), or morphine (30 mg/kg). The same measurements were taken in animals given beta-endorphin (1.0 mg/kg) in combination with naloxone or saline pretreatment and d-amphetamine (15 mg/kg) or saline post-treatment. Morphine alone had a biphasic effect on thermoregulation, but did not affect d-amphetamine-induced hypothermia. Activity scores were decreased by morphine, in both d-amphetamine and saline treated animals. The thermal response of rats to beta-endorphin alone was variable, depending on dosage, but all 3 dosages partially blocked the hypothermic effect of d-amphetamine. Naloxone blocked the thermal effects of both beta-endorphin and d-amphetamine. Motor activity tended to be decreased by naloxone, regardless of amphetamine treatment, but beta-endorphin tended to increase activity in amphetamine-treated animals and reduce it in saline-treated controls. In their actions on both thermoregulation and activity, naloxone and beta-endorphin appeared to interact independently with d-amphetamine, often producing effects in the same direction, but in combination, they tended to be mutually inhibitory.     

Potentiation by naltrexone of d-amphetamine-induced behavioral suppression and its reversal by clonidine

Rats were trained to perform a fixed ratio-15 operant for food reinforcement during a 30 minute daily session. Naltrexone, in doses up to 45 mg/kg administered 15 min before the behavioral session, failed to disrupt responding. However, 0.3 and 1.0 mg naltrexone/kg produced a dose related potentiation of the operant behavioral suppression induced by 1.0 mg d-amphetamine/kg injected immediately before the session. The naltrexone/d-amphetamine combination also produced excessive salivation and postural abnormalities not seen when either drug was administered alone. [A subsequent study indicated that the salivation induced by naltrexone in combination with d-amphetamine may require previous exposure to naltrexone and/or d-amphetamine.] Blockade of dopamine receptors with pimozide did not modify the interaction. Functional noradrenergic blockade with a low dose of clonidine significantly reversed the potentiated suppression, of operant behavior, as well as the excessive salivation and abnormal posture. These data suggest that there is an important noradrenergic component to the interaction of naltrexone with d-amphetamine. The impressive interaction of behaviorally inactive doses of naltrexone with a moderate dose of d-amphetamine reported here for rats may have clinical implications for detoxified opiate addicts maintained on naltrexone in antagonist therapy programs.     

The effect of an intruded event on peak-interval timing in rats: isolation of a postcue effect

The present experiment employed the peak-interval (PI) procedure to study the effect of an intruded cue on timing behavior. Rats were trained on a 30-s PI procedure with a tone cue. Subsequently, a 6-s flashing light was paired off-baseline with foot shock (Experiment 1) or presented alone (Experiment 2). Then, in test trials, the light cue was presented 9s prior to (before) or 3s after (during) the onset of the timing cue, or the light was omitted (probe). Results showed rightward shifts in peak time occurring on both before and during trials in both experiments. Peak shifts on during trials exceeded the reset prediction in Experiment 1. When PI functions for before and probe trials were normalized in peak rate and peak time, they superimposed better than when functions were adjusted additively along the time axis, suggesting that the light cue may engender a decrease in functional clock rate. The findings suggested that the intruded cue produced both intracue and postcue interference with timing that was enhanced by fear conditioning.     

Seasonal dynamics of sestonic protease inhibition: impact on Daphnia populations

Daphnia populations often show rapid microevolutionary adaptation to environmental changes. Here, we investigated the possibility that microevolution of Daphnia populations could be driven by natural sestonic Protease Inhibition (PI). We hypothesized that PI changes seasonally, which might lead to concomitant changes in tolerance to PI in a co-occurring Daphnia magna population. In order to test this, seston from a eutrophic pond was sampled regularly over two successive years. Extracts of these freeze-dried samples were used to determine their Inhibitory Potential (IP) on D. magna gut proteases. In the summer seston the IP against chymotrypsins exceeded that of spring seston 200-fold. In order to test for possible impacts on the co-existing D. magna population, we isolated clones before (spring) and after (fall) the peak of the IP. Microsatellite analyses revealed that the two subpopulations were genetically distinct. Individual exposure of three clones from each population to varying concentrations of a cyanobacterium that contains chymotrypsin inhibitors revealed a decrease in population and somatic growth rate for each clone, but no seasonal effects on Daphnia’s tolerance. In order to include maternal effects, we conducted a multi-clonal competition experiment on various cyanobacterial concentrations. However, no evidence for seasonally increased tolerance of D. magna to dietary protease inhibitors could be found.     

Tolerance to d-amphetamine: behavioral specificity.

In a Y-maze exploratory task mice tend to enter that compartment which was least recently visited (spontaneous alternation). Low doses of d-amphetamine (1.0 mg/kg) reduce alternation to chance levels, while high doses (10.0 mg/kg) result in animals successively visiting only two compartments of the Y-maze (perseveration). Following daily d-amphetamine injection (1.0 or 10.0 mg/kg) over a 30 day period tolerance to the d-amphetamine induced perseveration was observed; however, chronic amphetamine treatment did not modify the locomotor stimulating effects of d-amphetamine or the reduction of alternation to chance levels produced by low doses of the drug. It was hypothesized that tolerance to d-amphetamine occurs exclusively to behaviors mediated by norepinephrine.     

Dynamics of temporal control in rats: the effects of a brief transition in interval duration

Five rats lever-pressed for liquid reinforcers delivered according to a fixed-interval (FI) reinforcement schedule, where the interval requirement changed at an unpredictable point within a session. In a short square wave (SSW) condition, eight 30-s intervals were intercalated in a series of 120-s intervals so that the intervals changed from 120 to 30 s then back to 120 s. In a long square wave (LSW) condition the intervals changed from 120 to 480 s then back to 120 s. We observed rapid temporal control of post-reinforcement wait time duration by the IFI duration in the SSW condition only: Wait times decreased significantly during a transition to shorter (30 s) intervals; whereas wait times did not reliably increase during a transition to longer (480 s) intervals. Furthermore, in the SSW condition, wait time in post-transition intervals was shorter than that observed during pre-transition intervals. The results show that rats' wait times are sensitive to moment-to-moment changes in interval duration and that the dynamics depend on the direction in which the intervals change.     

Pharmacological manipulation of sincalide (CCK-8)-induced suppression of feeding

The current study involves an investigation of the possible neurotransmitter systems involved in the ability of exogenously administered sincalide (cholecystokinin octapeptide, CCK-8) to suppress feeding. Male rats previously trained to obtain food either during a daily 3-hr session, or conditioned to obtain food pellets on a fixed-ratio or fixed-interval schedule of reinforcement, were treated IP with CCK-8, following pretreatment with representative drugs of several pharmacological classes. Pretreatment with phenoxybenzamine, tolazoline, yohimbine, morphine, haloperidol or picrotoxin reduced the efficacy of CCK-8. However, pretreatment with naloxone or clonidine potentiated the suppressant action of CCK-8 on feeding. Propranolol, diphenhydramine, cimetidine, atropine, d-amphetamine, fenfluramine or diazepam pretreatment either had no effect or no consistent action in altering the activity of CCK-8. The ability of CCK-8 to suppress feeding was not altered by subacute treatment with the anorectics, d-amphetamine or fenfluramine, using a regimen known to induce tolerance. These data indicate that CCK-8 exerts a different mechanism of action than that of fenfluramine or d-amphetamine, and furthermore, that noradrenergic, dopaminergic, GABAergic or endogenous opioid systems either mediate or can modify the effect of CCK-8 on feeding.     

The effect of intruded events on peak time: the role of reinforcement history during the intruded event

Pigeons were studied in an extension of a study by Aum et al. [Aum, S., Brown, B.L., Hemmes, N.S. 2004. The effects of concurrent task and gap events on peak time in the peak procedure. Behav. Process. 65, 43-56] on timing behavior under a discrete-trial fixed-interval (FI) procedure during which 6-s intruded events were superimposed on peak-interval (PI) test trials. In Aum et al., one event consisted in termination of the timing cue (gap trial); the other was a stimulus in the presence of which subjects had been trained to respond under an independent random-interval (RI) schedule of reinforcement (concurrent task trial). Aum et al. found a disruption of timing on concurrent task trials that was greater than that on gap trials. The present study investigated history of reinforcement associated with intruded events as a possible explanation of this earlier finding. After training to peck a side key on a 30-s PI procedure, discrimination training was conducted on the center key in separate sessions; red or green 6-s stimuli were associated with RI 24s or EXT (extinction) schedules. During testing under the PI procedure, three types of intruded events were presented during probe trials--the stimulus associated with the RI (S+) or EXT (S-) schedule during discrimination training, or a gap (termination of the side-keylight). Intruded events occurred 3, 9, or 15s after PI trial onset. Effects of reinforcement history were revealed as substantial disruption of timing during the S+ event and relatively little disruption during the S- event. Intermediate effects were found for the gap event. Results indicate that postcue effects are at least partially responsible for the disruptive effects of the S+ event.     

Acute low-intensity microwave exposure increases DNA single-strand breaks in rat brain cells

Levels of DNA single-strand break were assayed in brain cells from rats acutely exposed to low-intensity 2450 MHz microwaves using an alkaline microgel electrophoresis method. Immediately after 2 h of exposure to pulsed (2 μs width, 500 pulses/s) microwaves, no significant effect was observed, whereas a dose rate-dependent [0.6 and 1.2 W/kg whole body specific absorption rate (SAR)] increase in DNA single-strand breaks was found in brain cells of rats at 4 h postexposure. Furthermore, in rats exposed for 2 h to continuous-wave 2450 MHz microwaves (SAR 1.2 W/kg), increases in brain cell DNA single-strand breaks were observed immediately as well as at 4 h postexposure. © 1995 Wiley-Liss, Inc.     

An investigation of tolerance to the actions of leptogenic and anorexigenic drugs in mice

This study compared the effects of chronic administration of anorexigenic drugs on weight loss in mice. Tolerance to the effects of peripheral anorexigenic peptides, viz. cholecystokinin-octapeptide and bombesin, developed rapidly. Morphine, cocaine and dehydroepiandrosterone-sulfate caused weight loss and appeared similar to d-amphetamine in mechanisms of action. A high dose of fluoxetine (25 mg/kg) proved to be a potent leptogenic agent but was also associated with death in some animals. A lower dose of fluoxetine (5 mg/kg) was associated with the development of tolerance. Calcitonin, a potent anorexigenic agent, did not produce weight loss and tolerance to its anorectic effect had developed by 10 days. Animals varied widely in their individual responsiveness to a given drug. Peripheral administration of peptide YY caused weight loss. We conclude that acute or chronic effects of agents on food intake do not necessarily predict effects on body weight. However, neurotransmitters that enhance feeding centrally appear to cause weight loss when administered peripherally.     

半自然水域中长江江豚春季昼间活动节律的观察

2004年2~4月,采用岸边定点和流动观察的方法对生活在半自然夹江水域中的5头长江江豚(Neophocaena phocaenoides asiaeorientalis)昼间活动节律进行了初步研究。结果表明,成年长江江豚春季昼间行为表现为摄食所占比例最多,为62.5%;其次是玩耍、移动和休息,分别为16.4%、10.7%和8.6%;其他行为最少,为1.8%。摄食高峰在8:30~16:30时,玩耍和移动也主要发生在该时段,休息存在1个高峰期。主要原因是人工投喂和在春季中午前后鱼群活动剧烈,长江江豚主要活动是摄食行为,而休息行为多发生在早晨和傍晚。     

柑橘大实蝇羽化出土及橘园成虫诱集动态研究

【背景】柑橘大实蝇是柑橘类果树上的重要害虫。预测该虫的羽化出土进度、掌握成虫发生动态是指导橘同成虫期防治的重要依据。【方法】本研究通过在25℃恒温、室内常温和室外网室3种条件下饲养柑橘大实蝇的蛹,以逐日观察成虫羽化出土数量;在重庆武隆、四川江油等5个地区共设置240个麦克菲尔（MePhail）诱集器,以糖酒醋液和水解蛋白为诱饵诱集成虫,得到柑橘大实蝇成虫羽化出土的逐日数量和橘园成虫诱集的逐期数量。【结果】用逻辑斯带模型拟合成虫羽化出土和橘园成虫诱集动态,结果表明,成虫的始盛期、高峰期和盛末期在25℃恒温条件下分别为4月25日、28日和30日,盛期的持续时间为6d;在室内常温条件下分别为5月3日、7日和10日,盛期的持续时间为8d;在室外网室条件下分别为5月8日、14日和18日,盛期的持续时间为11d;橘园诱集成虫分别为6月2日、14日和26日,盛期的持续时间为25d。【结论与意义】随着羽化期温度的提高,柑橘大实蝇羽化出土期提前,历期缩短,羽化整齐。虽然网室成虫羽化和橘园成虫诱集都处于室外条件,但后者的始盛期、盛期和盛末期比前者分别迟了36、30和22d。因此,建议采用室外网室饲养蛹的方法监测柑橘大实蝇成虫的发生期,若仅凭橘园诱集成虫的数据,因其滞后性十分明显,对指导柑橘大实蝇成虫防治的意义不大。     

Critical role of the hypothalamic pituitary adrenal axis in amphetamine-induced sensitization of behavior

Behavioral sensitization can be observed with repeated administration of amphetamine where the intensity of motor stimulation increases over time. The process of sensitization has been well characterized, however, the neurochemical mechanisms that are critical for the development of sensitization are not known. In the present study, the role of the hypothalamic pituitary adrenal axis (HPA) in the development of behavioral sensitization to amphetamine was explored by pretreating rats with an intravenous administration of an antiserum to corticotropin-releasing factor in a volume that has been shown to block significantly stress- and cocaine-induced activation of the HPA. Four groups of eight rats were pretreated intravenously with either heparinized saline or CRF antiserum and subcutaneously with saline or d-amphetamine in a balanced design. The rats were then returned to their home cages and left undisturbed for seven days after which they were given three consecutive behavioral tests with saline SC, 0.75 mg/kg d-amphetamine SC, and 3.0 mg/kg d-amphetamine SC. The rats pretreated with intravenous CRF antiserum showed a significant attenuation of the development of d-amphetamine-induced sensitization but the antiserum did not alter the magnitude of the behavioral response to the initial, sensitizing dose of d-amphetamine. These results suggest that activation of the hypothalamic pituitary adrenal axis may be of critical importance to the development of behavioral sensitization to amphetamine.