摘要:

The effects of H1-antagonists, such as tripelennamine, chlorpheniramine and pyrilamine, on the discriminative stimulus effects of cocaine and methamphetamine in rats were examined. Rats were trained to discriminate between cocaine (10 mg/kg, Lp.) or methamphetamine (1.0 mg/kg, Lp.) and saline, with responses maintained under a fixed-ratio 10 (FR10) schedule of food delivery. In generalization tests, tripelennamine generalized to the discriminative stimulus effects of cocaine and methamphetamine, while chlorpheniramine only generalized to cocaine. These generalizations of tripelennamine and chlorpheniramine were attenuated by the dopamine receptor antagonist haloperidol. Furthermore, tripelennamine and chlorpheniramine, but not pyrilamine, potentiated the discriminative stimulus effects of cocaine and methamphetamine. These results suggest that some H1-antagonists possess cocaine- and/or methamphetamine-like discrminative stimulus effects which may be mediated by the dopaminergic system, and as a result the discriminative stimulus effects of cocaine and methamphetamine were potentiated by these H1-antagonists.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Repeated amphetamine treatment results in sensitisation both of its behavioural effects, and of its dopamine (DA)-releasing effects on which the former largely depend. Understanding the nature of the sensitised response may help to explain behaviours which emerge only with repeated treatment, such as particular stereotypies and effects on social behaviour in animals, and links between these effects and the emergence of dependence and psychotic symptoms in humans. We show here that a single pretreatment with amphetamine (1 mg/kg) is sufficient to sensitise the locomotor response to amphetamine challenge (1 mg/kg) 24 h later. We have usedin vivomicrodialysis in the nucleus accumbens in unrestrained rats to demonstrate a corresponding potentiation in the DA response; the marked increase in accumbens dialysate DA following amphetamine (to 427% of basal) was significantly potentiated (to 675% of basal) by the pretreatmeat, without any alteration in the basal DA. There was also no change in the expected reduction in DA metabolites. Replacement of perfusate calcium by magnesium left the response to acute amphetamine challenge substantially unaffected, as expected from previous reports; however, the potentiation of the DA response by amphetamine pretreatment was prevented. Similarly the potentiated response was attenuated by administration of ondansetron, a 5HT-3 antagonist, (0.01 mg/kg) before each amphetamine treatment. The ability of amphetamine to disrupt latent inhibition (LI), which Is also disrupted in acute schizophrenia, has been suggested to provide a model of schizophrenia linking underlying cognitive deficits with the DA theory of the disorder. Since LI is disrupted by two systemic administrations of amphetamine 24 h apart, but not by one, the present results are consistent with the concept that It is the calcium, and hence impulse, dependence of increased accumbal DA release, rather than its magnitude, which is critical for the disruption of LI.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The effects of response requirement and small doses of methadone on human oral self-administration of methadone were examined. Three methadone maintenance patients stabilized at a dose of 80 mg methadone per day were recruited as subjects. Completing a response requirement, fixed ratio (FR) of 32, 64 or 128 responses (FR32, FR64, FR128) on one button dispensed 10 ml of drug solution. Completing the equivalent response requirement on a second concurrently available response button dispensed 10 ml of vehicle. The opportunity to respond was unavailable until the drug or vehicle had been consumed. Each 10 ml of drug solution contained methadone doses of 0.027, 0.054 or 0.108 mg/ml. The frequency of deliveries was limited so that subjects could not ingest more than 54 mg of methadone; the difference between the 80 mg daily methadone dose and the methadone consumed in session was administered 30 min post-session. At FR64 and FR128 the frequency of deliveries decreased, at the 0.054 and 0.027 nag/ml doses, relative to the frequency of deliveries at FR32. The amount of methadone consumed Increased with increases in methadone dose and decreased with increases in FR size. These results demonstrate the reinforcing effects of small unit doses of methadone. This procedure provides a sensitive baseline for examining effects of other pharmacological interventions on methadone ingestion in humans.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The effects of acute administration of chlordiazepoxide (2.5 and 5.0 mg/kg, i.p.), nicotine (0.05,0.1 and 0.4 mg/kg, s.c.) andd-amphetamine (0.5 and 1.0 mg/kg, i.p.) on rat potentiated startle were investigated. Chlordiazepoxide, 2.5 and 5.0 mg/kg, attenuated potentiation of startle, indicating an anxiolytic profile, although the effect of the higher dose was less marked and was accompanied by a reduction in overall startle response, probably reflecting drug-induced sedation. Nicotine at doses of 0.05 and 0.4 mg/kg had no significant effects in this test. However, 0.1 mg/kg nicotine eliminated potentiation of startle (in two separate experiments), an action comparable to that of 2.5 mg/kg chlordiazepoxide.d-Amphetamine at doses of 0.5 and 1.0 mg/kg did not significantly influence potentiation of startle. The results suggest that nicotine has an anxiolytic profile in the potentiated startle paradigm which is not due to its psychostimalant properties.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

People who drink alcohol are more likely to smoke, and experiments have shown that alcohol can increase cigarette smoking. However, it is not clear why alcohol consumption should increase smoking. To address this issue the current experiment looked at the effects of alcohol on a range of behavioural and subjective measures intended to assess the reward value of smoking. These included a preference test carried out after subjects had smoked cigarettes of one colour after consuming alcohol, and cigarettes of another colour after consuming non-alcoholic drinks. In the preference test, subjects were offered the choice of smoking the alcoholic or non-alcoholic drink-paired cigarette. It was hypothesised that if alcohol increased the reward value of smoking, subjects would choose to smoke the alcohol-paired cigarette. Consumption of alcohol increased the length of time people spent smoking, increased the number of puffs taken on each dgarette, and increased the amount of tobacco burnt There were also strong subjective effects, with subjects looking forward more to smoking after alcohol and reporting greater smoking satisfaction after alcohol However, subjects did not show a preference for the cigarettes they had smoked after alcohol.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The mechanism by which buprenorphine reduces opioid self-administration in humans and animals is generally thought to be through its opioid agonist effects. Buprenorphine, given acutely i.v. to three rhesus monkeys 30 min prior to a session in which a range of doses of either alfentanil or heroin was available, produced dose-related decreases in the potency of both opioid agonists. The effects of buprenorphine were generally surmounted by increasing the dose/injection of alfentanil or heroin available for self-administration, indicating that buprenorphine was acting as an opioid antagonist in this situation. These data suggest that at least part of the effectiveness of buprenorphine in reducing opioid administration by human opioid users may be via its opioid antagonist properties.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

In order to examine whether tolerance develops to the discriminative stimulus and reinforcing effects of ketamine, rats were trained either to discriminate ketamine (10 mg/kg) from saline or to self-administer ketamine (1.1 mg/kg/injection), and then treated with chronic ketamine (32 rag/kg), administered i.p. every 8 hours for 7 days. No shift in the dose-response curve for either paradigm was obtained following this chronic regimen. However, following a 2-week rest period in which animals had no exposure to ketamine, the dose-response curve was shifted two-fold to the left, indicating increased sensitivity to the drug. Reinstatement of training shifted the dose-response curve back to the right in both paradigms. These results suggest that tolerance to the discriminative stimulus and reinforcing effects of ketamine develops during training. Examination of the self-administration training data support this assumption, since inter-reinforcer time decreases, reflecting an increase in ketamine intake over training sessions.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Rats were tested in an open field, a “sniffing box” and an eight-arm maze, to examine in detail the behavioural changes induced by morphine (10 mg/kg, i.p.) and MK-801 (0.1 mg/kg, i.p.), either alone or in combination, during a 10 day treatment and subsequent drug challenges. In addition to locomotion, a number of other behaviours such as sniffing, rearing and exploration were examined. After morphine challenge, sensitised locomotion and rearing were found in the open field, and sensitised sniffing and turning were observed in the sniffing box. In addition, In the sniffing box, saline challenge produced significant conditioned sniffing and turning, and after a challenge with MK-801, sensitised sniffing and turning were seen in the group pretreated with morphine, suggesting a cross-sensitisation between morphine and MK-801 (but not vice versa). In the eight-arm maze, sensitised locomotion was found after morphine challenge. Morphine and MK-801 changed the preference for particular angles run during trials in a characteristic manner. In none of the behavioural measures was MK-801 able to block the development (and expression) of sensitisation to morphine. In several cases, rather, MK-801 enhanced the acute morphine effects. Sensitisation of sniffing suggests that sensitisation has also developed within the nigrostriatal dopamine system and not only within the mesolimbic dopamine system, as is generally discussed in the context of the most commonly assessed behaviour, locomotion. This finding argues for the additional use of the sniffing box in sensitisation experiments.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Acute (10 mg/kg, i.p.) and chronic (10 mg/kg/day, i.p. for 10 days) diazepam treatments decreased hippocampal dialysate 5-HT (but not 5-HIAA) concentrations in freely moving rats, suggesting decreased availability of 5-HT to receptors. Twenty-four hours after the last chronic diazepam injection, hippocampal dialysate 5-HT did not differ from that in vehicle-treated rats. However, although reduced 5-HT availability often Increases postsynaptic 5-HT receptor-mediated responses, the anxiogenic effect of m-chlorophenylpiperazine (mCPP), which is mediated by the activation of postsynaptic 5-HT2creceptors, was not increased (as indicated by the elevated plus-maze test) when given 2 days after 10 days of chronic diazepam, in intact rats. Nevertheless, concurrently in that test, significantly increased anxiety occurred after withdrawal from chronic diazepam (10 mg/kg/day x 10 days). The results suggest that benzodiazepine withdrawal-induced anxiety is not mediated by changes in 5-HT2creceptor sensitivity, and may be independent of the beazodiazepine-induced reduction of 5-HT release in the rat hippocampus.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The present study examined the subjective, psychomotor and reinforcing effects of 10%, 20%, 30% and 40% nitrons oxide in oxygen in 16 healthy volunteers using a choice procedure in which sampling (e.g. 20% nitrous oxide and oxygen-placebo) and choice trials (e.g. 20% nitrous oxide vs. oxygen-placebo) were within the same session. Across the four-session study, nitrous oxide dose was varied. Nitrous oxide in a dose-related manner altered subjective effects (e.g. increased visual analog scale ratings of “high”, “stimulated” and “tingling”) and decreased performance on the Digit Symbol Substitution Test. 10%, 20%, 30% and 40% nitrous oxide were chosen over oxygen by 6, 7, 7 and 8 subjects, respectively. We conclude that nitrous oxide across a range of subanesthetic doses did not function as reinforcer in the majority of subjects tested.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID