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1.
The effects of chlorpromazine (2 mg/kg) on the acquisition of lever-pressing behaviour for food rewards have been examined in rats. The drug greatly impaired performance during acquisition but, during a subsequent non-drug testing session, performance was only slightly below that of controls trained and tested under saline; giving the drug to control rats before the testing session markedly impaired performance. It was concluded that chlorpromazine acted mainly on factors, such as attention or motor ability, which were important both during and after acquisition, and that it had little action on central learning processes. Dissociation of learning between drugged and non-drugged states did not occur; changes in drug state even increased responding during extinction, but not during continuous reinforcement. Simple depressant effects of chlorpromazine on attention and motor ability do not seem adequate to account for this, and a further possibility is that the changes in drug state minimised emotional responses elicited by the omission of rewards.  相似文献   

2.
Extinction of a food reinforced habit results in an increase in the variability of the response learned in acquisition and in the appearance of previously suppressed competing responses. The purpose of the present study was to examine the effects of chronically administered diazepam (0.0, 1.5, 3.0, or 6.0 mg/kg, IP, –30 min) or 10% ethanol (0.0, 1.0, 1.5, or 2.0 g/kg, IP, –15 min) on such behavioral variability in the extinction of radial maze performance. Eight groups of food deprived rats (n=6) were given one of the forementioned doses for 2 sessions of baseline, 18 sessions of acquisition, and 5 sessions of extinction. In acquisition, eight rewards of two food pellets were obtained on each of three trials in each session. The food well at the end of each arm was rebaited when empited by the animal, consequently an entry into any arm was reinforced. In base-line and extinction no food was available in the maze. Each session consisted of three 10-min trials. In extinction, compared to treatment with vehicle, both diazepam and ethanol treatments decreased the rate of the instrumental response, arm entry, and increased the variability of the instrumental response and of competing responses. Only the effects of the drugs on the competing responses in extinction were greater than those observed in acquisition. It was concluded that the interference-reduction model of drug action best described the magnitude of the drug effects and the variability-reduction model best predicted the direction of the effects.  相似文献   

3.
Mice given one-trial passive avoidance training were examined 24 hours later for retention of the acquired response. Testing was carried out with subjects given either chlorpromazine or saline injections before the test session. Three chlorpromazine doses (0.5, 2.0, and 3.5 mg/kg) were used, and three injection times (10, 90, or 180 min before testing). Chlorpromazine was found to impair the expression of the acquired response, both by depressing its initial elicitation and also by apparently facilitating extinction. A second experiment confirmed that extinction rate was indeed increased. A clear dosage effect was observed but injection time was not important in determining the drug's effect. Further experiments were undertaken to clarify the interpretation of the drug's action; in particular, the possibility that the effects might have been caused by a dissociation of learning between the training and test situations was examined. It is suggested that the elevated extinction rates observed during testing when subjects were given chlorpromazine represents a temporary effect resulting from the reduced stimulus control of behaviour. Permanent effects of pre-test drug administration were noted on the initial expression of the learned response.  相似文献   

4.
Summary The present experiment was designed to test the inhibitory effect of chlorpromazine upon avoidance responding as a function of CS-US interval length. Three dosages of chlorpromazine, 0.00, 0.75, and 1.5 mg/kg and three CS-US intervals, 5, 10, and 15 sec constituted the 3 × 3 factorial design. Each subject (S) served in only one of the nine conditions. Male albino rats were given avoidance training and extinction in a Miller-Mowrer shuttlebox. The CS (damped house buzzer) preceded the US (electric shock) by the interval designated by the condition. On escape trials, both CS and US terminated when S jumped the barrier separating the compartments. On avoidance trials, CS was response-terminated and the US eliminated for that trial. During extinction each group was subdivided into two equal groups, one receiving 0.00 mg/kg and the second 0.75 mg/kg of chlorpromazine.Analysis of the total number of acquisition avoidances indicated no dosage effect but a significant linear dosage interval interaction. Further analysis revealed no differences between levels at the 5 or 10 sec CS-US interval. At the 15 sec CS-US interval, however, there was a linear decrement in number of responses with increase in dosage, thus indicating that increasing CS-US interval increased the inhibitory effect of chlorpromazine relative to control conditions. These findings were inconsistent with interpretations of the chlorpromazine effect based on the inhibition of the motor component. Rather these results were interpreted as supporting the notion that attenuation of avoidance under chlorpromazine is associated with loss of attention or arousal.This work was done with the support of USPHS, NIMH Grant MH 03312.NIH Career Award Program 2-K 3-GM-1759.  相似文献   

5.
Summary Twenty-four rats received 54 differential instrumental conditioning trials (single stimulus presentation) in which an approach to one stimulus was reinforced and to a second was nonreinforced, followed by 24 extinction trials in which approaches to either were nonreinforced. Twelve animals received a 20 mg/kg amobarbital sodium injection (i. p.) ten minutes before the six daily trials and 12 received an equal volume isotonic saline injection. The drug did not affect terminal response latency to the reinforced stimulus but resulted in shorter latencies to the nonreinforced stimulus in both initial acquisition and extinction. These data support the hypothesis that amobarbital at this dose level has a specific attenuating effect on those anticipatory processes related to aversive emotion-producing events.This research was supported by National Science Foundation grants GB 1505 and GB 4373 to J. R. Ison.  相似文献   

6.
We explored how stimulation of GABAA receptors at different times during conditioned taste aversion (CTA) acquisition or extinction influenced extinction. In Experiment 1, rats acquired a CTA to 0.3% saccharin-flavored water (SAC) when it followed an injection of lithium chloride (LiCl; 81.0 mg/kg, i.p.). Following conditioning, rats received extinction training in which the GABAA agonist muscimol (1.0 mg/kg, i.p.), or control (saline) injections, were administered either before or after each extinction trial. Muscimol hindered extinction when administered after extinction trials. Muscimol's inhibitory effects may have impeded extinction learning by disrupting synaptic mechanisms required to consolidate information experienced during extinction training. In Experiment 2, we studied the effects of muscimol on CTA acquisition and subsequent extinction. Rats received muscimol (1.0 mg/kg, i.p.) either before or after CTA conditioning trials. Following CTA acquisition, all rats were given CTA extinction training without muscimol administration. All groups developed CTA, but the group that received muscimol before CTA conditioning trials extinguished rapidly in comparison to other treatment groups. Differences between muscimol's effects on CTA conditioning and CTA extinction indicate that fear conditioning and extinction involve, to some degree, different neuronal mechanisms.  相似文献   

7.
In order to study the relationship between pharmacologically induced hippocampal theta rhythm and resistance to extinction of instrumental responding, three groups of rats were trained on a discrete-trial FR 10 schedule of reinforcement, one group receiving injections of physostigmine (producing hippocampal theta rhythm) and the other two groups saline injections. This was followed by a noinjection phase for all three groups during which the schedule of reinforcement remained unchanged. In the extinction phase the drug-acquisition group and one of the saline acquisition groups received saline injections, while the remaining group received drug injections. Following extinction allSs went through reacquisition and a second extinction without any injections. The findings were that if physostigmine was administered during acquisition resistance to subsequent extinction was enhanced, but if it was administered during the extinction phase extinction was accelerated. The second acquisition and extinction did not yield any significant drug effects.The research herein reported was part of a dissertation submitted in partial fulfillment of the requirements of the Ph.D. at the University of Texas, and was supported by the National Science Foundation Grant GB-14990 X to Dr. Abram Amsel. Thanks are due to Dr. A. B. Combs, Department of Pharmacology, for his assistance with the pharmacological aspects of the study.  相似文献   

8.
The effects of amphetamine administration on the partial reinforcement extinction effect (PREE) at one trial a day, were examined. Two groups of rats were trained to run in a straight alley. The continuously reinforced (CRF) group received food reward on every trial. The partially reinforced (PRF) group was rewarded on a quasirandom 50% schedule. All animals were then tested inextinction. dl-Amphetamine 1.5 mg/kg was administered in a 2×2 design, i.e., drug-no drug in acquisition and drug-no drug in extinction. The PREE, i.e., increased resistance to extinction exhibited by PRF animals as compared to CRF animals, was obtained in animals that received saline in acquisition, independently of drug treatment in extinction. In contrast, amphetamine administered in acquisition abolished the PREE irrespective of drug treatment in extinction. In addition, amphetamine administered in extinction alone increased resistance to extinction in PRF animals.  相似文献   

9.
Responding was established in squirrel monkeys under a modified progressive ratio schedule of IV d-amphetamine or cocaine self-administration. Substitution of saline for the drug solutions resulted in extinction of the self-administration behavior. IV injections of certain doses of d-amphetamine or cocaine, immediately prior to test sessions in which response-contingent saline infusions were delivered, reinstated the rate and pattern of responding observed during sessions in which drug was self-administered. Presession IV injections of several doses of pentobarbital or chlorpromazine failed to consistently reinstate responding. These results were interpreted in terms of the discriminative control of drug self-administration behavior by the current drug state of the subject.  相似文献   

10.
Hungry rats (n = 40) were given 60 training trials in a multiple continuous reinforcement (CRF) schedule under either drug (p-chloroamphetamine, 3.5 mgkg i.p.) or placebo (saline) conditions. A comparable 60 trial testing phase followed in which half of the subjects continued under the training injection conditions and the other half were switched to the alternative injection. Drugged subjects displayed slightly inferior discrimination performance in training as a result of elevated responding in extinction. No differences between groups were obtained on CRF performance. In the testing phase, extinction performance was similarly affected by both concurrent testing and prior training phase conditions. The data suggest that p-chloroamphetamine administration results in a selective disruption of responding to stimuli correlated with nonreward and that this effect tends to persist for long periods of time. The results are consonant with other reports of disinhibition resulting from brain serotonin depletion.  相似文献   

11.
Summary Scopolamine was tested for effects on acquisition of a passive-avoidance problem. First mice were given four trials 24 hours apart on a step-off apparatus. Various dose levels of the drug were studied. For one group the drug was injected i.p. 20 minutes prior to each trial, in the other immediately after. Doses of 5.0 mg/kg and higher greatly interfered with the acquisition of the response, but only when injected prior to the trial. These results failed to indicate any direct effect of the drug on the learning process. The only time the drug affected the behavior was when the animal was under its influence at the time of testing.A second experiment was conducted in which mice were trained as before but pre-injection of 5.0 mg/kg of scopolamine was used. However, the mice were injected with the drug on only some of the trials. In all, six groups were studied, and their performance compared with a group that had received scopolamine on all trials and with one that received saline on all trials. When the data were examined for evidence of dissociation, it was clear that it was not present. Further analysis showed that animals which had learned, as indicated by their performance on the early trials conducted when they were not drugged, failed to show evidence of memory when given additional trials after being drugged. This outcome clearly indicated that a major effect of scopolamine was on the performance of the animal. Also, animals which had received 1 or 2 trials while drugged and given additional trials in the nondrugged state, showed a rapid increase in latency on succeeding trials equal that of animals which had not been drugged at all.These results, in light of other research, indicate that the effect of scopolamine on this type of learning task does not appear to be through a modification of the consolidation process.A preliminary report of Experiment I was made at the Southeastern Psychological Association Annual Meeting in Atlanta, Georgia, April, 1967. Supported by NIMH Grant No. MH 12770-01 to the senior author.  相似文献   

12.
There is a significant degree of individual variability in response to drugs of abuse. A goal of behavior genetic studies has been to determine the extent to which observed heterogeneity in drug use can be attributed to genetic and environmental factors and to identify the neurobiological factors involved in vulnerability. Recent hypotheses regarding the predictive value of spontaneous locomotor activity in the acquisition of drug-reinforced behavior are amenable to testing using a behavior genetics approach. Genetic differences in locomotor response to a novel environment were determined in naive and catheterized Lewis, F344, NBR and ACI rats. Operant drug-reinforced behavior was examined in a 23h access paradigm in which each lever press by a rat produced a 1mg/kg injection of morphine with a 30s timeout period (FR 1:TO 30"). Acquisition (7 days), extinction (6 days) and reacquisition (7 days) of morphine self-administration behavior was investigated in all four inbred strains. Large genetic differences in the rate of acquisition and extinction of morphine self-administration were found. Lewis rats responded at high rates beginning in the first two days, whereas F344 rats initially responded at low rates and responding increased gradually over seven days. NBR and ACI rats responded at intermediate levels. When vehicle was substituted for drug there was a significant effect of genotype on the rate of extinction; F344 and ACI increased responding to greater than 175% of drug-response levels, whereas the Lewis response rate decreased gradually and NBR response rate decreased immediately during the first several days. When drug was available again, rates of reacquisition did not differ from original acquisition rates. Drug maintained significantly greater amounts of behavior than vehicle in the Lewis, F344 and NBR rats and was thus shown to serve as a positive reinforcer in these three strains under these conditions. There was a significant genetic correlation among strains between drug intake during the first five days of acquisition and spontaneous locomotor response to a novel environment in catheterized rats. Only the ACI rats showed a significant within-strain correlation. The positive relationship between rate of acquisition of self-administration behavior and locomotor activity suggests that these two traits are influenced by common or closely linked genes. To this end, the neurobiological substrates that mediate spontaneous locomotor behavior under these environmental conditions may act, in part, as a template for determining the neurobiological substrates that mediate the relative rate of acquisition of morphine-taking behavior under these conditions.  相似文献   

13.
Summary The effects of chlorpromazine on conditioned avoidance behaviour were compared in a group of rats which were exposed to trials either immediately or one hour after drug administration. The results showed that the sensitivity to chlorpromazine, determined on the basis of 100 trials starting 60 minutes after the injection of the drug, is significantly less when the rats were exposed to trials just from the moment of the drug injection than if there were no trials during the 60 minutes preceding the determination. The importance of the behavioural arousal provoked by the experimental procedure in the effects of chlorpromazine is discussed.Research fellow of the Istituto Superiore di Sanità, Roma.  相似文献   

14.
Rats were rewarded by food for running in a straight runway with short (15 sec) intertrial intervals. On the final day, animals were subjected to either 14 extinction trials or 14 rewarded trials. During acquisition, half of each group had been injected once daily for 15 days with propranolol (5 mg/kg IP), the remainder with saline vehicle. All animals were killed immediately after the final trial and the cerebral cortex taken for noradrenaline assay and radioligand binding to beta- and alpha 2-adrenoceptors. Propranolol increased running times early in extinction; this effect was replicated in a second experiment. Neither the drug injections nor the extinction procedure affected neurochemical measures. However, the rate of extinction correlated positively with both beta- and alpha 2-adrenoceptor number. Although consistent with the theory that beta-adrenoceptors are involved in adaptation to stress, these results differ from our previous findings. The relationship between beta-adrenoceptor number and the response to stress may depend on the severity of the stress.  相似文献   

15.
Pigeons obtained food by making 4 responses on 3 keys in a specified sequence, e.g., left, right, center, right. All 3 keys were the same color throughout the response sequence. Under the learning condition, the four-response sequence was changed from session to session. After learning (within-session error reduction) had stabilized, this baseline of repeated acquisition was used to assess the effects of varying doses of d-amphetamine and chlorpromazine. For comparison, the drug tests were also conducted under a performance condition in which the four-response sequence was the same from session to session. Increases in total errors and pausing were obtained at the largest dose of each drug under both the learning and performance conditions. Under the learning condition, the error rate decreased across trials within each session, but the degree of negative acceleration was less in the drug sessions than in the control sessions. In contrast, under the performance condition, the error rate was relatively constant across trials, but was higher in the drug sessions than in the control sessions.  相似文献   

16.

Rationale

We have shown previously, using an animal model of voluntary ethanol intake and ethanol-conditioned place preference (EtOH-CPP), that exposure to chronic psychosocial stress induces increased ethanol intake and EtOH-CPP acquisition in mice.

Objective

Here, we examined the impact of chronic subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol-induced reinstatement of CPP.

Methods

Mice were conditioned with saline or 1.5 g/kg ethanol and were tested in the EtOH-CPP model. In the first experiment, the mice were subjected to 19 days of chronic stress, and EtOH-CPP extinction was assessed during seven daily trials without ethanol injection. In the second experiment and after the EtOH-CPP test, the mice were subjected to 7 days of extinction trials before the 19 days of chronic stress. Drug-induced EtOH-CPP reinstatement was induced by a priming injection of 0.5 g/kg ethanol.

Results

Compared to the single-housed colony mice, CSC mice exhibited increased anxiety-like behavior in the elevated plus maze (EPM) and the open field tests. Interestingly, the CSC mice showed delayed EtOH-CPP extinction. More importantly, CSC mice showed increased alcohol-induced reinstatement of the EtOH-CPP behavior.

Conclusion

Taken together, this study indicates that chronic psychosocial stress can have long-term effects on EtOH-CPP extinction as well as drug-induced reinstatement behavior and may provide a suitable model to study the latent effects of chronic psychosocial stress on extinction and relapse to drug abuse.  相似文献   

17.
Four groups (N=8) of rats received five 15-trial sessions of one-way avoidance training. Each trial was signaled by a ten-second tone stimulus and shock followed on a random 67% of the trials. Prior to each session two groups were injected with 1.0 mg/kg of the neuroleptic pimozide and the other two groups received vehicle injections. The pimozide groups failed to acquire the avoidance response although they escaped readily when shock was presented, and the vehicle groups acquired the avoidance response. Three 15-trial nondrug test sessions followed. For one group that had been trained under pimozide and one vehicle group, shock continued to follow the tone on 67% of the test trials. The remaining two groups were tested in extinction, i.e., shocks were no longer presented. Both groups that were trained under pimozide showed gradual acquisition of the avoidance response in the first nondrug test session. The group that received vehicle during training and shock during testing continued to avoid whereas the other vehicle group showed extinction of the avoidance response across test sessions. The acquisition of responding in the extinction group trained under pimozide indicated that the association of environmental stimuli with shock had been learned during training in spite of the failure to avoid. The gradual acquisition of the response indicated that this group had failed to learn the appropriate motor response during training. These results support previous observations of associative learning in animals treated with neuroleptics but further suggest that dopamine plays a role in mechanisms of response learning.  相似文献   

18.
Intravenous self-administration of the short-acting benzodiazepine midazolam was assessed in rats under conditions of unlimited access to the drug (24 hr/day). Evaluation of the temporal pattern of responding within a session revealed that maximal responding occurred during the dark phase of the 12 hr light/dark cycle. Upon attaining stable rates of responding for midazolam, the rats were tested under extinction conditions (saline). Responding progressively decreased with repeated extinction sessions. Over the course of subsequent reacquisition sessions responding increased, such that asymptotic levels of responding were similar to, or greater than, the rates obtained during the initial acquisition phase. In addition, the total number of sessions required to approach asymptote were fewer than during the initial acquisition phase. Thus, rats given continuous access to midazolam exhibited reliable and stable rates of intravenous self-administration of this short-acting benzodiazepine.  相似文献   

19.
The effects of acute chlorpromazine treatment were assessed using a complex operant test battery (OTB) containing five tasks thought to depend upon processes associated with short-term memory and attention [delayed-matching-to-sample (DMTS)], color and position discrimination [conditioned position responding (CPR)], motivation [progressive ratio (PR)], time perception [temporal response differentiation (TRD)], and learning [incremental repeated acquisition (IRA)]. Adult male rhesus monkeys were tested 15 min after IV injection of saline or chlorpromazine (0.010, 0.030, 0.100, or 0.175 mg/kg). Behavioral endpoints measured included percent task completed, response rate or latency, and response accuracy. The order of task sensitivity to disruption by chlorpromazine was TRD = PR = IRA = DMTS = CPR in which sensitivity was defined as a significant alteration in any aspect of task performance. Chlorpromazine slowed response rates in all tasks except TRD but did decrease accuracy in that task. These effects were similar to those noted in previous studies of acute chlorpromazine treatment. Specific motoric effects suggested decreased task initiation at doses that left general motor ability intact. This finding is similar to that noted in parkinsonism caused by chronic chlorpromazine treatment.  相似文献   

20.
De Vry  Jean  Koek  Wouter  Slangen  Jef L. 《Psychopharmacology》1984,83(3):257-261
Rats were trained to discriminate between fentanyl (0.04 mg/kg) and saline in a two-lever procedure. Using a FR 10 schedule of food reinforcement, drug-induced differences between the number of reinforcers obtained under fentanyl and saline conditions were observed. The effect of eliminating these differences on the outcome of generalization tests was investigated by different manipulations. In one group (N=10), the FR 10 schedule used during saline sessions was changed to FR 6 during drug sessions. In a second group (N=12), saline sessions ended after the number of reinforcers obtained was equal to the number obtained during the preceding drug session. A control group (N=10) was trained using a FR 10 schedule under both conditions. Elimination of differences in reinforcement frequency 1) accelerated the acquisition of the discrimination, 2) diminished response bias, 3) flattened the slope and reduced the ED50 value of generalization gradients of fentanyl, morphine and sufentanil and 4) increased the ED50 value of naloxone in antagonizing 0.04 mg/kg fentanyl. It is concluded that the unconditioned effects of 0.04 mg/kg fentanyl on response rate in a FR 10 procedure lead to differences between saline and drug sessions which contribute to the apparent discriminative stimulus properties of fentanyl.  相似文献   

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