摘要:

Despite its ubiquitous consumption in the natural environment, caffeine has not been a reliable reinforcer in laboratory settings. The reinforcing effects of caffeine are greater in caffeine-dependent subjects relative to non-dependent subjects, but the mechanism underlying this difference remains unclear. We hypothesized that deprivation from caffeine would produce alterations in subjective ratings of stimuli commonly associated with caffeine consumption. Specifically, we hypothesized that hedonic ratings of She coffee taste would be selectively enhanced following caffeine deprivation. Twelve regular caffeine users received acute doses of caffeine (300 mg) or placebo after 33 h of caffeine deprivation or non-deprivation. They rated the taste of coffee and sucrose, saccharin, and quinine solutions on intensity, bitterness, sweetness, pleasantness, and unpleasantness. Contrary to our hypothesis, subjects' ratings of She pleasantness of the coffee taste were not significantly altered by caffeine deprivation. However, subjects' ratings of the bitterness and sweetness of the coffee taste and ratings of the sucrose solution were altered by caffeine. Implications of these data for caffeine self administration are discussed.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Latent inhibition (LI) is a measure of retarded conditioning to a previously presented non-reinforced stimulus, that is unpaired in schizophrenic patients and in rats treated with amphetamine. Neuroleptic drugs are known to produce two effects in this paradigm: to antagonize amphetamine-induced disruption of LI, and to facilitate the development of LI when administered on their own. The present experiments tested the effects on LI of the new neuroleptic, sertindole. The experiments used a conditioned emotional response procedure in rats licking for water, consisting of three stages: pre-exposure, in which the to-be-conditioned stimulus (a tone) was repeatedly presented without being followed by reinforcement; conditioning, in which the pre-exposed stimulus was paired with reinforcement (a foot shock); and test, in which LI was indexed by degree of suppression of licking during tone presentation. In Experiment 1 the effects of 0.31, 1.3 and 5.0 mg/kg sertindole were assessed following pre-exposure to 40 non-reinforced tones. Experiment 2 tested the effects of 5 mg/kg on LI following pre-exposure to 10 non-reinforced tones. Experiment 3 investigated antagonism of amphetamine-induced disruption of LI by 5.0 mg/kg sertindole. The results demonstrated that sertindole (5.0 mg/kg) possesses a neuroleptic-like profile in the LI model: it facilitates the development of LI and antagonizes amphetamine-induced disruption of LI.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The effects of μ agonists fentanyl, methadone and morphine and K agonist U50,488 on behavior maintained by negative reinforcement were determined. Rats were trained on concurrent schedules in which pressing one lever postponed shock on a Sidman avoidance schedule and pressing the other lever produced signaled periods of timeout from avoidance on variable-ratio schedules. All of the μ agonists decreased responding maintained by timeout from avoidance at doses that increased or did not affect avoidance rates. The K agonist U50,488 decreased response rates in some rats, but increased responding in others. In no case was a selective reduction in responding on the timeout lever produced by U50,488. Thus, the previously reported selective decreases in timeout responding by morphine are also produced by μ agonists fentanyl and methadone, but not by K agonist U50,488.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The dependence potential of the putative 5-HT1Aagonist anxiolytic S-20499 was assessed in rats in a study in which the benzodiazepine chlordiazepoxide (CDP) was used as a “positive control”. S-20499 was administered b.i.d. (at 10.00 and 16.00 h) for 21 days, at constant doses of either 0.5, 3 or 18 mg/kg i.p. Subsequently, spontaneous withdrawal from S-20499 was studied over 7 days. Acutely, S-20499 decreased body weight and food intake and complete tolerance developed to these effects. When S-20499 was withdrawn there was no evidence of any effect on body weight or food intake. CDP was also administered b.i.d. (at 10.00 and 16.00 h) for 21 days at doses escalated from 10 to 30 mg/kg i.p, CDP differed from S-20499 in some of its acute effects, stimulating body weight and food intake. In contrast to S-20499 withdrawal, CDP withdrawal induced weight loss and aphagia. Acutely, S-20499 resembled CDP in inducing hypothermia. Full tolerance developed to this effect of both drugs. However, only CDP withdrawal induced hyperthermia. Thus S-20499 appeared to be devoid of benzodiazepine-like dependence potential after administration for a relatively long period of time, at doses that are substantially greater than “anxiolytic doses” in rats.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The effects of dopamine (DA) antagonists that act on either the D1 site (SCH 39166), the D2 site (eticlopride), or both sites non-selectively (cis-flupenthixol) were evaluated for their effects on behavior maintained by cocaine or alfentanil in rhesus monkeys. Each of these drugs suppressed rates of responding maintained by cocaine or alfentanil. Larger doses of each of the DA antagonists were necessary to suppress cocaine- as opposed to alfentanil-maintained responding, suggesting that cocaine but not alfentanil was able to antagonize the rate-suppressing effects of the antagonists. There was little evidence, under these conditions of acute administration, that the DA antagonists modified the reinforcing effects of either cocaine or alfentanil. This would have been observed by an antagonist-induced increase in the ED50of the reinforcing drugs and, although such an increase was seen occasionally with cocaine, it was never statistically significant. The effects of rate-suppressing doses of each of the antagonists on directly observable behavior indicated a rapid onset and relatively short duration of action of intravenously administered SCH 39166 and eticlopride. cis-Flupenthixol had a much slower onset of action. Each of the DA antagonists produced similar increases in measures of sedation and relaxation. These data suggest very similar behavioral effects of DA antagonists that act selectively on D1 or D2 receptors or act non-selectively on both DA receptors.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Interactions between the effects of cocaine and caffeine have been demonstrated in tests of motor activity and drug discrimination. Since both drugs are widely consumed by humans, the present study was undertaken to determine whether a similar interaction between the reinforcing effects of these drugs could be demonstrated. Experienced cocaine self-administering rats were treated with caffeine either as an i.p. injection (20.0 mg/kg) prior to each self-administration test or as a co-administered drug within the infusion syringe (0.25 mg/kg/infusion). Both of these routes of administration of caffeine increased the intake of low doses of cocaine. Since caffeine is not reliably self-administered by laboratory animals, these data suggest that caffeine potentiated the reinforcing effects of cocaine.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The extent to which drugs are consumed may be related to whether they are available in a closed or open economy. This study examined the effects of the “openness” of an economy on responding for cigarettes during a computer task and cigarettes earned. Using a within-subjects design, openness was manipulated by varying the number of free (unearned) cigarettes available to subjects during a 6 h post-task period. No free cigarettes were available during the “closed” economy session; 5 or 10 free cigarettes were available during the two open economy sessions. Subjects performed a concurrent random-ratio (RR) schedule task to earn points redeemable for cigarettes or money. The cigarette schedule varied within a session from RR1.3 to RR16. Throughout each session, money was concurrently available under an RR4 schedule. As the number of free cigarettes increased, fewer responses were made for cigarettes and fewer cigarettes were earned. A behavioral economic analysis of cigarette demand curves revealed that demand for cigarettes was equally elastic when subjects received 5 or 10 free cigarettes, but less elastic when they received no free cigarettes. We conclude that whether an economy is closed or open affects drug (cigarette) consumption in humans, but the degree of openness has limited effects.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

These studies were conducted in order to establish the dose dependency and relative peripheral versus central activity of four prototypical cholinergic antagonists on the rodent passive avoidance response, a widely used animal model of retention. Subcutaneous administration of 0.1 to 100mg/kg revealed a potency profile of scopolamine > atropine >> methylscopolarnine ≥ methylatropine for the impairment of passive avoidance responding. A series of neurological assessments of the doses used indicated that side effects alone were not sufficient to impair passive avoidance responding. Although inactive when delivered peripherally, methylatropine was able to produce retention deficits at 10 nmol (3.66 μg) when administered intracerebrally. To further evaluate whether systemic methylatropine could enter the central nervous system, either scopolamine or atropine was administered subcutaneously in mice and rats pretreated with 10–100 mg/kg methylatropine. The deficit-producing effects of scopolamine and atropine were abolished with methylatropine. Thus methylatropine is an exclusive peripheral antagonist; its ability to block the deficit-producing effects of scopolamine and atropine may occur through a change in blood brain barrier permeability or through uncharacterized pharmacokinetic properties.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Baboons were trained to discriminate either pentylenetetrazole (PTZ) or β-carboline-3-carboxylic acid ethyl ester (β-CCE) from the no-drug condition. Both drugs specifically bind sites in the γ-aminobutyric acid A (GABAA) receptor complex and decrease GABAergic transmission. β-CCE occasioned drug-lever responding in baboons trained to discriminate PTZ and vice versa. Flumazenil, the benzodiazepine receptor antagonist, blocked β-CCE. consistent with β-CCE's receptor binding activity. The azaspirodecanedione anxiolytics buspirone and ipsapirone produced full generalization in all baboons; gepirone and tandospirone yielded full generalization in some baboons and partial in others. These anxiolytics are inactive in the GABAAcomplex and potently bind 5-HT1Asites. A specific 5-HT1Aligand, 8-hydroxy-2-(di-n-propylamino)tetralin, produced generalization similar to gepirone and tandospirone, which show the most specific 5-HT1Abinding. The major azaspirodecanedione metabolite, 1-(2-pyrimidinyl)piperazine (an α2-adrenergic antagonist), occasioned the least drug-appropriate responding. Full generalization to buspirone and ipsapirone may have resulted from dopaminergic or α1-adrenergic activity combined with 5-HT1Aactivity. The molecular mechanism of the generalization profile for PTZ and β-CCE shown by the present results is unclear. The data may reflect altered relationships between GABAergic and serotonergic transmission, and altered stimulus effects of the training drugs, in the context of chronically decreased GABAergic transmission.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Loperamide (0.1–3.2 mg/kg i.p.) produced dose-dependent and complete suppression of writhing in the acetic acid-induced writhing assay in mice. Naltrcxone (NTX; 0.1–10.0 mg/kg s.c.) and its N-methylated derivative quaternary naltrexone (QNTX; 1.0 and 10.0 mg/kg s.c.) were roughly equipotent in antagonizing the antinociceptive effects of loperamide. In contrast, NTX was approximately 100-fold more potent than QNTX in antagonizing the antinociceptive effects of the classical mu agonist morphine. Furthermore, the antinociceptive effects of loperamide were not antagonized by central administration of the selective mu antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2(CTAP; 300 ng i.c.v.), or by systemic administration of either the kappa selective antagonist nor-binaltorphimine (nor-BNI; 32.0 mg/kg s.c.), or the delta antagonist naltrindole (NTI; 10.0 mg/kg s.c). These doses of CTAP, nor-BNI and NTI were effective antagonists of morphine, the kappa agonist U69,593 and the delta agonist BVV 373U86 [(±)-4-((R*)-a-((2S*5R*)-4-allyl-2,5-dimethyl-1-piperazinal)-3-hydroxybenzyl)-N,N-diethylbenzamide dihydrochloride], respectively. These results indicate that the antinociceptive effects of loperamide in mice are mediated, at least in part, by opioid receptors; however, these receptors are distinct from the opioid receptors mediating the effects of morphine, U69,593 and BW 373U86. These results are consistent with the hypothesis that loperamide produces its antinociceptive effects by acting, at least in part, at peripheral opioid receptors.

ISSN:0955-8810    

出版商:OVID    

年代:1994

数据来源: OVID