摘要:

A mutually exclusive choice procedure was used to evaluate the reinforcing effects of caffeine in eleven normal subjects with histories of regular caffeine consumption (mean 256 mg/day). Subjects participated for 24 weeks; each week consisted of three consecutive daily sessions (two sampling days followed by a choice day) during which subjects were required to abstain from dietary sources of caffeine. On each sampling day subjects ingested four capsules, one every 2 h. Capsules contained placebo on one sampling day and caffeine (50 or 100 mg/capsule) on the other sampling day. Placebo and caffeine were associated with different color-coded capsules. At the beginning of the choice day subjects chose one of the two color-coded capsules they wished to take on that day; they were required to ingest one capsule and, thereafter, they could ingest up to six additional capsules of the same color throughout the day. Across subjects and dose, caffeine was chosen over placebo on 80% of choice occasions; nine of 11 subjects (82%) chose caffeine on more than 70% of choice occasions and caffeine choice was replicable despite changes in capsule colors across blocks. This is the first study in a relatively uncontrolled outpatient context to demonstrate significant caffeine reinforcement in the majority of normal subjects.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The effects of NMDA and non-NMDA glutamate receptor antagonists were evaluated on social recognition of adult male rats. Adult animals were injected (s.c.) with drug or saline immediately after the initial exposure to a juvenile male, 21–24 days old, and re-exposed to the same or to a novel juvenile 30 min later. If the lime spent by animals in social investigation during re-exposure to the same juvenile was comparable with the time measured during the initial exposure and with the time of animals re-exposed to a novel juvenile, the effect of a drug was designated as amnesia. Such an effect was found in adult animals administered 1 and 1.5 mg/kg phencyclidine, 0.1 mg/kg dizocilpine, 2.5 mg/kg CPP, and 4 mg/kg CGS 19755. Amnesic effects were observed at doses not affecting motor performance. No amnesic effect was produced by CNQX and NBQX. (2.5, 5 and 10 mg/kg). These results show that while recognition capacity in adult male rats is disrupted by several NMDA antagonists, non NMDA antagonists do not interfere with short-term retention of individual odours. This suggests that NMDA glutamate receptors may be involved in the processing of socially relevant olfactory information.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The widespread use of benzodiazepines and caffeine makes their combined use inevitable. The purpose of the present experiment was to assess the acute effects of lorazepam (0, 2.8 and 5.6 mg/70 kg) and caffeine (0, 250 and 500 mg/70 kg), alone and in combination, on human learning, performance and self-reports. Subjects were nine healthy, male volunteers. Subjects received all possible combinations according to a Latin Square design. Lorazepam administered alone dose-dependently disrupted learning and performance on the Repeated Acquisition and Performance procedure and Digit Symbol Substitution Test (DSST), and increased subject ratings of sedation. Caffeine administered alone did not affect learning, performance or subject ratings to a statistically significant degree. Caffeine attenuated lorazepam-induced decrements in learning and performance on the Repeated Acquisition and Performance procedure and DSST. Consistent with the learning and performance measures, caffeine offset lorazepam-induced increases in subject ratings of sedation. These results demonstrate that caffeine generally attenuates the behavioral and self-reported effects of lorazepam on a variety of performance measures. An important extension of these findings would be to test the combined effects of lorazepam and caffeine in other behavioral paradigms such as drug self-administration.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

This experiment investigated the hypothesis that nicotine-induced regional release of noradrenaline contributes to the improvements in radial maze performance following nicotine treatment in rats with lesions to the forebrain cholinergic projection system (FCPS), by examining whether pretreatment with the noradrenergic β-receptor antagonist propranolol abolished the facilitative effects of nicotine. After S-AMPA (8.0 mM) lesions to the nuclei of origin of the FCPS in the nucleus basalis and medial septal areas, rats displayed long-lasting impairment in long-term reference and short-term working memory in both spatial (place) and associative (cue) radial maze tasks. Performance of control and lesioned rats was assessed after administration of nicotine (0.1mg/kg), propranolol (either 0.5 or 5.0 mg/kg) and both treatments. Nicotine reduced working memory error rates in lesioned animals, but did not affect the performance of controls. Propranolol dose-relatedly increased error rates in both control and lesioned animals. Adverse effects were more marked in controls, all four types of error being increased under the high dose of propranolol, whereas in lesioned rats significant increases in error rates above baseline were confined to working memory. The low dose of propranolol, in conjunction with nicotine, abolished the improvement in working memory seen with nicotine alone in lesioned rats. However, under joint treatment with the high dose, the substantial increases in working memory error rates seen in lesioned rats after propranolol alone were reduced to baseline level. In controls, reduction in errors to baseline was seen only in the cue task; place task errors remained significantly elevated. These results suggest that both cholinergic depletion and noradrenergic blockade exert disruptive effects on cognition, but that these effects are largely independent, since an additive or interactive mechanism would be predicted to produce greater disruption, following noradrenergic blockade, in lesioned rather than in control animals. Although facilitative effects of nicotine were abolished with the low dose of propranolol, the results further suggest that these effects are independent of release of noradrenaline, since nicotine continued to reduce errors in control and lesioned animals following blockade of β receptors with the high dose of propranolol.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

This study assessed the reinforcing and subjective effects of methylphenidate in a group of 35 adults (15 females and 20 males) with no history of drug dependence. A discrete-trial choice procedure was used to assess the reinforcing effects of a single oral dose of methylphenidate selected to produce a moderate subjective response in each subject (range 20–40 mg). A number of variables (gender, current and past drug use. personality, and baseline mood and arousal) were examined in an attempt to identify sources of variability in drug response. Methylphenidate was chosen on 28% of occasions. In the group as a whole, methylphenidate had no effect on ratings of drug liking, but did increase ratings indicative of “positive” mood, CNS stimulation and anxiety. Within-subject variability in methylphenidate choice was related to variability in subjective response to the drug across choice trials. Methylphenidate choice was also associated with between-subject differences in prior opioid use and several personality dimensions. When compared with the results of a prior study of the same design with d-amphetamine, these results suggest that methylphenidate produces a somewhat different profile of subjective effects, and may be a less efficacious reinforcer than d-amphetamine.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Physical dependence on cocaine has not been fully characterized or definitively identified. Since behavioral changes are typically not observed after cocaine withdrawal in animal studies, we sought to amplify or reveal any such changes in behavior by administration of the dopamine agonist apomorphine. C57BL/6J mice were tested for behavioral effects (climbing, gnawing, and locomotor activity) of apomorphine at various times after acute administration of cocaine. When tested at a time when most of the administered cocaine had disappeared from brain and when behavioral effects of cocaine had dissipated, at 2 and 4 h post cocaine administration, effects of apomorphine on gnawing were increased 4-fold. This dopaminergic hypersensitivity was induced by acute treatment with doses of 15 mg/kg cocaine and higher. Effects of apomorphine were not enhanced at later time periods (6 to 24 h after cocaine), indicating a rapid waning of the dopaminergic hypersensitivity. Hypersensitivity to apomorphine was not further augmented by 8 days of daily cocaine injections. Cocaine did not influence climbing and hypomotility induced by apomorphine 4 h after its injection, demonstrating selectivity in the behavioral expression of the dopaminergic hypersensitivity. Further, cocaine did not induce sensitization to its own effects indicating that the hypersensitivity to apomorphine was not due to a typical sensitization phenomenon. The results of these experiments demonstrate a short-lived dopaminergic supersensitivity after termination of the acute effects of a single high dose of cocaine, the implications of which remain to be discovered.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The aim of the present study was to combine in vivo microdialysis in the rat with behaviour in the social interaction test in order to investigate changes in both 5-HT release and cyclic AMP (cAMP) efflux in the ventral hippocampus with simultaneous measurement of behaviour. Exposure of the rat to a 10 min period of social interaction with an unfamiliar partner in a brightly lit, unfamiliar arena resulted in an increase in extracellular 5-HT and extracellular cAMP in the ventral hippocampus. Pretrcatment with diazepam (1 mg/kg i.p.) 30 min prior to the social interaction test significantly inhibited the increases in both extracellular 5-HT and cAMP while significantly increasing the amount of time the pair of rats spent in active social contact over the 10 min period. During the 30 min prior to the social interaction test diazepam reduced basal levels of 5-HT, but had no effect on the basal efflux of cAMP. Pretreatment with a selective 5-HT1Aantagonist, WAY 100135 (5 mg/kg s.c), 30 min prior to the social interaction test, significantly potentiated the increase in extracellular 5-HT observed in saline-treated rats during the social interaction test. In contrast, WAY 100135 pretreatment significantly attenuated the increase in extracellular cAMP observed in saline-treated rats during the social interaction test but had no effect on the time spent in active social contact between pairs of rats. The results suggest that social interaction results in activation of a post-synaptic 5-HT receptor (5-HT1Aor 5-HT6/5-HT7) coupled to adenylate cyclase but that this receptor is not responsible for the aversion-induced behaviour. Furthermore antagonism of the 5-HT1Asomatodendritic autoreceptor under conditions of 5-HT neuronal activation, but not under basal conditions, potentiates 5-HT release.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Previous experiments showed that acute administration of the angiotensin converting enzyme (ACE) inhibitor, ceronapril, shares with neuroleptic drugs an ability to enhance latent inhibition (LI), which consists of retardation in conditioning to a stimulus as a consequence of its prior non-reinforced pre-exposure. Experiment 1 tested whether ceronapril would produce a neuroleptic-like effect in the partial reinforcement extinction effect (PREE) at one trial a day. The PREE refers to the increased resistance to extinction observed in animals trained on a partial reinforcement (PRE) schedule compared with those trained on a schedule of continuous reinforcement (CRF). Two groups of rats were trained to run in a straight alley. The CRF group received food reward on every trial. The PRF group was rewarded on a quasi-random 50% schedule. All animals were then tested in extinction in which no reward was given. Ceronapril at a dose of 0.05 mg/kg was administered in a 2 × 2 design, with drug or no drug in acquisition and drug or no drug in extinction. Rats receiving vehicle in acquisition showed a PREE, regardless of their drug treatment in extinction. In contrast, ceronapril administered in acquisition attenuated the PREE irrespective of drug treatment in extinction, by both increasing resistance to extinction in CRF animals and decreasing resistance to extinction in PRF animals. This pattern of results does not resemble that produced by neuroleptics. The PREE procedure necessitated repeated administration of ceronapril, whereas the previous demonstrations of neuroleptic-like enhancement of LI have been obtained with acute administration. Experiment 2 therefore tested the effects of chronic ceronapril administration on LI. Under these conditions, ceronapril abolished LI. The results are discussed in relation to the antipsychotic, anti-anxiety and cognitive-enhancing effects formerly attributed to ACE inhibitors.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Six healthy human volunteers (ages 18 to 24) acquired a triazolam (0.32 mg/70 kg) vs placebo discrimination under a standard, two-response drug discrimination procedure. Dose-effect curves were then determined for triazolam (0.1–0.56 mg/70 kg), lorazepam (0.75–3.0 mg/70 kg) and buspirone (7.5–30 mg/70 kg) under a novel response procedure that provided a response alternative for drugs unlike triazolam or placebo (i.e. a novel-appropriate response). Triazolam dose-dependently increased triazolam-appropriate responding but did not occasion any novel-appropriate responding, Lorazepam dose-dependently increased triazolam-appropriate responding in four of six subjects, but at least one dose also occasioned novel-appropriate responding in three subjects. Buspirone dose-dependently increased novel-appropriate responding, although three of six subjects also made triazolam-appropriate responses following some dose(s). All three drugs comparably increased self-reported sedation. Self-reported effects did not differentiate triazolam from lorazepam whereas only buspirone increased “bad” self-reports, and did not increase “liking” and “good” self-reports. The results suggest that the novel response procedure enhanced the pharmacological selectivity of human benzodiazepine discrimination and may help interpret partial generalization under two-choice drug discrimination procedures. The results also add to the evidence of a close relationship between the discriminative stimulus and self-reported effects of drugs.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Experiments were performed to investigate the effects of microinjections of the 5-HT1Aagonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), the non-selective 5-HT1agonist 5-carboxamidotryptamine (5-CT) and the GABAAagonist muscimol into the midbrain raphe nuclei, on behaviour maintained by a differential reinforcement of low rate (DRL) 20 schedule of food reinforcement. Following acquisition of responding under the DRL20 schedule, in which responses were reinforced only if they occurred at least 20 s after the previous response, two groups of rats were prepared with a stainless steel guide eannula aimed at either the dorsal raphe nucleus or the median raphe nucleus. Injections of 8-OH-DPAT and 5-CT into the median raphe dose-dependently increased responding and reduced the number of reinforcers earned, leading to a net reduction in response efficiency from 45% to approximately 27% (5 μg 8-OH-DPAT) and 22% (375 ng 5-CT). Both drugs appeared to shift the frequency distribution of inter-response times (IRTs) towards shorter IRTs, and lowered the mean IRT. These effects were not observed after dorsal raphe injections of either drug. This pattern of results, together with results obtained in other paradigms measuring response inhibition, suggests that suppression of the activity of median raphe 5-HT neurones induces deficits in the ability to withhold responding. Muscimol increased responding, decreased the number of reinforcers earned and reduced response efficiency after both dorsal raphe and median raphe injections. These effects were more pronounced following median raphe injections, and were of considerably greater magnitude than those observed following treatment with the 5-HT agonists. Muscimol injected into the median raphe lowered the mean IRT, and increased the frequency of short duration IRTs. Thus, stimulation of GABAAreceptors within the median raphe induces a pattern of behavioural disruption in the DRL task, that is more severe than that resulting from selective inhibition of 5-HT neural activity. The effects of muscimol probably arise from a general behavioural activation, rather than a specific deficit in the ability to withhold responding.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID