摘要:

Classical conditioning and behavioural sensitisation of motor activity induced with cocaine (10 mg/kg, i.p.) were examined using an unbiased two-compartment conditioned place preference (CPP) procedure. Habituation of the rats to the testing environment prior to training was varied (i.e. either the rats were habituated to the environment for three 30 min sessions or they were not) in order to examine a possible influence of latent inhibition on conditioned locomotion or behavioural sensitisation. Furthermore, rats were either trained with an explicit CS+ (cocaine-paired compartment) and CS — (vehicle-paired compartment), or else they were trained with no barrier between the compartments (effectively a single-compartment procedure with no explicit CS —) in order to examine a possible influence of stimulus change (training rats while confined to one compartment, but testing with no barrier between compartments). On a drug-free test day with free access to both compartments, rats previously exposed to cocaine in one compartment (CS+) and vehicle in the second compartment (CS —) spent more time in the CS+ compartment (conditioned place preference). However, under no circumstance was the rate of motor activity higher in the CS+ compartment than in the CS — compartment, as would be expected if cocaine-induced motor activity was classically conditioned to contextual cues. Whether or not increased activity extinguished with repeated drug-free exposures to previously drug-paired contexts depended on habituation experience. In addition, both habituation and current access to compartments (free or restricted) determined the presence of post-extinction sensitisation to a challenge dose of cocaine (7.5 mg/kg). Classical conditioning and non-associative sensitisation, independently or together, cannot account for this pattern of results.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The present study evaluated the intravenous self-administration of four substituted phenethylamines, using a substitution procedure in baboons. Baboons were trained to self-inject 0.32 mg/kg/injection cocaine under a fixed-ratio (FR) schedule, with a 3 h timeout following each injection. Doses of (±)-N-ethyl-3,4-methylenedioxyamphetamine HCI (MDE), (±)-N-hydroxy-3,4-methylenedioxyamphetamine HCI (N-OH-MDA), (+)-N-N-dimethylamphetamine HCI (NNDMA), and 4-bromo-2,5-dimethyoxy-β-phenethylamine (BDMPEA) and their vehicles were substituted for cocaine for 15 or more successive days. High doses of MDE and N-OH-MDA maintained self-injection; however, NNDMA and BDMPEA self-injection was less consistent. NNDMA did not reliably maintain self-injection, whereas one or more doses of BDMPEA maintained self-injection in each of three baboons. Intermediate to high doses of all four compounds decreased food pellet intake maintained under a FR schedule of reinforcement on a different lever. In some baboons, high doses of N-OH-MDA, NNDMA and BDMPEA produced signs of behavioral toxicity (e.g. cyclic pattern of self-injection, behavioral agitation, stereotypical movements) that were similar to those previously observed after administration of high doses of classic psychomotor stimulants such asd-amphetamine; however, the severity and profile of this behavioral toxicity differed between compounds. Thus, the present study documents both similarities and differences in the behavioral profiles of these four phenethylamines.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Keypecking by 12 pigeons, maintained by a fixed-ratio 30 schedule of food presentation, was decreased in rate by acute pre-session injections of cocaine in a dose-dependent manner, with larger doses producing more disruption. A constant dose of cocaine was then injected prior to every session for 40 days. Some subjects received a relatively small dose, some received a medium-sized dose, and others received a large dose. Subsequently, dose-effects were reassessed via once-weekly probe injections, with every other session continuing to be preceded by injection of the daily dose of cocaine. Then a different dose of cocaine was administered daily for 40 more days, after which the dose-effect function was redetermined in like manner. In general, tolerance to cocaine-induced response-rate reductions was most likely to develop when (a) the repeatedly-administered dose of cocaine was relatively small (even without acute effect on keypecking) and (b) the subject's keypecking was disrupted by smaller doses of cocaine in the initial dose-effect assessment. Tolerance was generally observed as a shift in the dose-effect function that, in several cases, could be eliminated by increasing the magnitude of the daily administered dose. In addition, every subject's rate of keypecking following saline injections was lowered after daily exposure to cocaine. These results (a) are partially consistent with the reinforcement-loss account of tolerance to cocaine-induced behavioral disruptions, and (b) support previous observations of withdrawal symptoms following cessation of extended exposure to cocaine.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Modification of naloxone-precipitated withdrawal symptoms by drugs acting on α-adrenoceptors was investigated in morphine-dependent mice. Clonidine (0.05–1 mg/kg) attenuated most withdrawal symptoms, but potentiated withdrawal hypothermia. Jumping was attenuated by doses of clonidine up to 0.3 mg/kg, but markedly potentiated by 1 mg/kg. Prazosin (0.05 mg/kg) neither had effects of its own, nor influenced those of clonidine. Both yohimbine (0.5–5 mg/kg) and idazoxan (1–10 mg/kg) potentiated naloxone-precipitated withdrawal symptoms. When tested against a low dose of clonidine (0.2 mg/kg), idazoxan dose-dependently reduced the suppressive effects of clonidine on jumping, “wet dog” shakes, burrowing and body-weight loss but potentiated the hypothermic response of clonidine. Yohimbine similarly reduced the suppressive effect of clonidine on body-weight loss and potentiated its hypothermic response, but unlike idazoxan, it did not influence the inhibition by clonidine of “wet dog” shakes, and markedly reversed the suppression of jumping and burrowing into potentiation. Yohimbine and idazoxan also differed with respect to their antagonistic profile against a high dose of clonidine (1 mg/kg). Yohimbine further aggravated the potentiation of jumping by clonidine, reduced the effect on body-weight loss and reversed the suppression of burrowing by clonidine. On the other hand, idazoxan markedly reduced the potentiation of jumping by clonidine, and reversed its effect on “wet dog” shakes and burrowing. These findings indicate that clonidine has a biphasic effect on jumping, and disclose differences in the antagonistic profiles between yohimbine and idazoxan. The results suggest that in addition to α2-adrenoceptors, non-adrenergic imidazoline receptors sensitive to clonidine and idazoxan but not to yohimbine may modulate the expression of morphine withdrawal symptoms.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Rats bilaterally implanted with cannulae in the CA1 region of the dorsal hippocampus and/or in the amygdaloid nucleus, in the entorhinal cortex, and in the posterior parietal cortex, were trained in a step-down inhibitory avoidance task. At various times after training (immediately, 30, 60 or 90 min) they received, through the cannulae, 0.5 μl microinfusions of saline or of 5.0 μg of APS dissolved in saline. A retention test was carried out 24 h after training. Retention test performance was hindered by AP5 given into hippocampus, amygdala, or both hippocampus and amygdala immediately but not 30 min post-training. The drug was amnestic when given into the entorhinal cortex 30, 60 or 90 min after training, or into the parietal cortex 60 or 90 min after training, but not at earlier times. The findings suggest a sequential entry in operation, in the post-training period, of NMDA-receptor mediated mechanisms involved in memory processing; first in hippocampus and amygdala, 30 min later in entorhinal cortex, and 30 min later in posterior parietal cortex.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Calcium (Ca2+) channels appear to be involved in the regulation of ethanol (EtOH) intake, as indicated by the effectiveness of both L—type Ca2+channel antagonists and agonists in reducing EtOH intake in animals. The present study was aimed to investigate rewarding/aversive and discriminative stimulus effects of the Ca2+channel agonist BAY k 8644, a compound showing pronounced anti—alcohol effects in rats. Therefore, a series of conditioned taste aversion (CTA), conditioned place preference (CPP) and two—lever drug discrimination (DD) experiments were conducted in Wistar rats, with (±)—BAY k 8644 and its enantiomers. After i.p. application, (±)—BAY k 8644 (0.0625—1 mg/kg), (—)-BAY k 8644 (0.125—1 mg/kg) and (+)-BAY k 8644 (2.5–20 mg/kg) all induced a dose-dependent CTA. The minimal effective doses (MED) for (±)-, (—)- and (+)—BAY k 8644 were 0.25, 0.25 and 10 mg/kg, respectively. In a CPP study, however, (±)-BAY k 8644 (0.25–2 mg/kg, i.p.) showed neither aversive nor rewarding stimulus properties. Rats were trained to discriminate (—)-BAY k 8644 (0.3 mg/kg, i.p.), the enantiomer acting as a high potency Ca2+channel agonist, from vehicle, in a two-lever DD procedure (ED50value: 0.05 mg/kg); full generalization: 0.1 mg/kg). The (—)-BAY k 8644 cue dose-dependently generalized to (±)-BAY k 8644 and (+)-BAY k 8644, the enantiomer acting as a low potency Ca2+channel antagonist, with ED50values of 0.06 and 0.28 mg/kg, respectively. Both (±)- and (+)-BAY k 8644 produced full generalization at 1 mg/kg, the latter compound showing an inverted U-shaped curve (i.e., this was the only dose showing < 80% drug lever selection). The stimulus patterns of BAY k 8644 and its enantiomers appear to resemble the anti-alcohol profiles of these compounds. Therefore, commonalities between the stimulus properties of the agonistic and antagonistic enantiomers might provide a clue for the mechanism underlying the anti-alcohol effects of L-type Ca2+channel antagonists and agonists.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Cigarette cravings were evaluated in a sample of moderately heavy smokers, using the Questionnaire on Smoking Urges (QSU), and a progressive-ratio (PR) operant procedure in which responding on a computer keyboard was reinforced by puffs on a cigarette, under a progressively increasing work requirement. Subjects were also exposed to musical mood-induction procedures: the induction and maintenance of depressed and elated mood states was confirmed by visual analogue scales and a mood questionnaire. Smoking did not alter mood state. However, relative to the elated condition, induction of a depressed mood caused increases in both QSU scores and measures of PR performance. The results provide the first experimental confirmation of a causal relationship between depressed mood and cigarette craving.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The impact of training dose on the characteristics of a discrimination maintained by a mixture of two dissimilar drugs has been investigated in order to refine this approach to the study of drug interactions. Three groups of rats (n= 10) were trained to discriminate mixtures of (+)-amphetamine (0.2–0.8 mg/kg) plus pentobarbitone (5–20 mg/kg) from saline, in a two-lever operant procedure with food reinforcement, with the ratio of the doses held constant (amphetamine: pentobarbitone, 1:25). Discriminations were acquired to an accuracy of 90–97%. There was full generalisation to amphetamine alone, but only in rats trained with mixtures of the smaller doses of the single drugs. There was partial generalisation when either apomorphine (50%) or nicotine (63%) was administered alone, and the magnitude of these responses was inversely related to the dose of mixture used for training. Doses of pentobarbitone half of those used for training produced little discriminative response when administered alone to rats trained with the two smallest doses of the mixture; the same doses of pentobarbitone increased responses to amphetamine or apomorphine in a more than additive manner. Strikingly, some doses of apomorphine and pentobarbitone that did not generalise when administered separately, produced full generalisation when administered together, but only in rats trained with the smaller doses of the mixture. In contrast, pentobarbitone did not enhance generalisation to nicotine in any group. It was concluded that, on the one hand, patterns of generalisation to single drugs followed an orderly pattern resembling those for discriminations established with single drugs. On the other hand, there was a complex pattern of generalization from one mixture to another; thus, altering the doses of drugs used for training markedly influenced discriminations of an abused drug mixture, but no simple rules to predict the influence of training dose have been ascertained.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Previous studies have demonstrated that the non-specific adenosine antagonist caffeine possesses both motor activating and rewarding properties in a place-conditioning paradigm. The present experiments were designed to determine the relative contribution of Al and A2 adenosine receptor subtypes to these effects. The A2 adenosine antagonist CGS 15943A (0.1–10.0 mg/kg) dose-dependently produced both a place preference and enhanced locomotor activity. In contrast, the A1 antagonist CPA (0.01–40.0 mg/kg) failed significantly to alter either behavioral measure. Both the Al receptor agonist CPA (0.01–10.0 mg/kg) and the A2 receptor agonist CGS 21680 (0.01–1.0 mg/kg) reliably decreased activity but failed to produce significant place conditioning. The increased activity produced by the A2 antagonist CGS 15943A (1.0 mg/kg) was attenuated by behaviorally active doses of either CPA or CGS 21680. The place preference produced by CGS 15943A (1.0 mg/kg) was attenuated by CPA and CGS 21680, at agonist doses that failed to produce place conditioning when administered alone. In general, the results suggested that although it is the A2 receptor subtype that participates in the establishment of place conditioning and enhanced activity, both receptors participate in the diffuse depressant effects associated with adenosine.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The ability of picrotoxin to antagonize selectively the effects of pentobarbital was investigated in pigeons and squirrel monkeys responding under a titrating matching-to-sample schedule of reinforcement. Under the titrating matching-to-sample baseline, the length of the delay changed as a function of the animal's matching accuracy. Picrotoxin (0.03–1 mg/kg) failed to alter significantly the matching accuracy of pigeons; however, rate of responding was markedly suppressed at a dose of 1 mg/kg. In squirrel monkeys responding under a similar schedule, picrotoxin (0.001–0.3 mg/kg) was without significant effect. Selected doses of picrotoxin in both pigeons (0.3 and 0.56 mg/kg) and squirrel monkeys (0.1 and 0.3 mg/kg) failed to shift the pentobarbital or diazepam dose-response curve for mean delay length to the right. However, in both species, picrotoxin shifted the dose-response curve for pentobarbital on rate of responding to the right. No such shift was observed for the effect of diazepam on rate of responding. In both species, the combination of picrotoxin and phencyclidine shifted the dose-response curves for phencyclidine on rate of responding, but not mean delay, downward and to the left, in an apparent additive manner. Thus, picrotoxin failed to produce a significant pharmacological antagonism of the effects of pentobarbital, diazepam or phencyclidine on matching accuracy. This failure to observe an antagonism of the effects of pentobarbital on matching accuracy, at doses of picrotoxin that antagonized the effects of pentobarbital on rate of responding, suggests that the effects of pentobarbital on matching accuracy and rate of responding are mediated by different receptor sites.

ISSN:0955-8810    

出版商:OVID    

年代:1996

数据来源: OVID