摘要:

The behavioural response to psychomotor stimulants is augmented with repeated exposure to these drugs. Enhanced stimulated dopamine overflow within the nucleus accumbens and amygdala has been found to accompany this behavioural sensitization. In the present experiment, rats received 2 mg/kg d-amphetamine or 1 ml/kg physiological saline once per day for 5 days. Five days later, a behavioural assay confirmed that prior repeated d-amphetamine treatment markedly enhanced the locomotor activating effects of a d-amphetamine (0.5 mg/kg, i.p) challenge. Training on a Pavlovian conditioning task began six days subsequently. In Stage 1, a stimulus (light or tone, S-) was presented negatively correlated with a sucrose reward. In Stage 2, presentation of the alternative counterbalanced stimulus (light or tone, S+) was paired with the availability of a 10% sucrose solution. There were no differences between the two groups in their response to the the S— stimulus. However, sensitized animals showed a selective enhancement in the acquisition of conditioned responding to S+, relative to vehicle-injected controls. No differences in behaviour were recorded during the prestimulus periods, nor during presentations of sucrose. Levels of activity within the operant chamber extraneous to alcove approach were also similar in both groups of animals. The conditioned instrumental efficacy of S+, relative to S— was assessed in Stage 3, in which stimulus availability was made contingent on a novel lever-pressing response. Both groups showed a similar preference for the S+ over the S- stimulus. Hence, rats sensitized by prior repeated d-amphetamine showed enhanced appetitive Pavlovian conditioning, without subsequent effect on conditioned reward efficacy. These data are discussed in light of possible changes in mesoamygdaloid dopamine functioning. Behav Pharmacot 1998; 9:299–308 © 1998 Lippincott-Raven Publishers.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

A response duration differentiation schedule, where rats depress a lever for between 1.0 and 1.3 s to obtain a food reward, provides a useful measure for detecting antidepressant activity. It is known that 5-hydroxytryptamineIA (S-HT1A) receptor agonists exhibit antidepressant-like activity in multiple animal models of depression, however, compounds selective for this receptor have not been tested in this model to date. Thus, the present study sought to determine the effect of the full 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the partial 5-HT1A agonist, buspirone, on responding in the response duration differentiation task. The effects of these drugs were compared to the effects of the non-specific serotonergic agonist, lysergic acid diethylamide (LSD); the phenothiazine, chlorpromazine; the atypical antidepressant, trazodone; and the non-selective S-HT1A antagonists, propranolol and alprenolol. It was found that propranolol, trazodone, and both the full (8-OH-DPAT) and partial (buspirone) 5-HT1A agonists produced increases in the mean response duration, which is typical of antidepressant activity. By contrast, with the exception of propranolol, compounds lacking antidepressant efficacy (e.g. chlorpromazine, LSD and alprenolol), failed to produce increases in mean response durations. Further, the effects of 8-OH-DPAT were inhibited by pretreatment with the S-HT antagonist, (-)-alprenoIol (3.0 and 30.0mg/kg i.p.) The results of this study provide further support for the suggestion that S-HIM agonists may be useful for the treatment of clinical depression and that these effects are specifically mediated by 5-HT1A receptors. Behav Pharmacol 1998: 9:309–318 © 1998 Lippincott-Raven Publishers.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The purpose of this experiment was to examine the substitution patterns produced by opioids with activity at the mu receptor in pigeons trained to discriminate the delta opioid BW373U86 from saline. A low dose of naltrindole (0.1 mg/kg) produced at least a 16-fold rightward shift in the dose—effect curve for the stimulus effects of BW373U86 (yielding a pKB = 7.9), whereas a relatively high dose of naloxone (1.0 mg/kg) produced only a 2-fold rightward shift (yielding a pKB = 5.6). The delta opioid SNC80 and the mixed mu/kappa opioids ethylketocyclazocine and ketocyclazocine substituted completely for the BW373U86 stimulus. Various opioids with activity at the mu receptor (levallorphan, [-)-cyclazocine, [-]-n-allylnormetazocine, morphine, butorphanol, nalbuphine, [+]-propoxyphene, etorphine, fentanyl) substituted partially for the BW373U86 stimulus. There was no relationship between the substitution patterns produced by these opioids and their relative intrinsic efficacy at the mu receptor, their relative selectivity for the mu receptor or their relative affinity for the delta receptor. Naloxone (1.0 mg/kg) was considerably more effective than naltrindole (0.1 mg/kg) in antagonizing the substitution patterns produced by etorphine, ethylketocyclazocine, ketocyclazocine and butorphanol, suggesting that these effects were not mediated by activity at the delta receptor. There was no evidence that these opioids antagonized the BW373U86 stimulus, suggesting that they were not functioning as low efficacy agonists at the delta receptor. The kappa opioids bremazocine and U50,488, as well as the non-opioids cocaine and pentobarbital, failed to produce appreciable levels of BW373U86 responding. The present findings indicate that in pigeons mu opioids most likely produce delta-like discriminative stimulus effects by activation of mu rather than delta or kappa receptors. Behav Pharmacol 1998; 9:319–328 1998 Lippincott-Raven Publishers.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The conditions under which a drug is administered often alter the behavioral effects of that drug. The present study examined the effect of changes in response dependence on the discriminative stimulus effects of ethanol. Six Long-Evans rats were trained to discriminate 1000 mg/kg, interperitoncal (i.p.) ethanol from saline. A dose—effect curve was then obtained using i.p. doses of 100, 320, 560, 1000, 1320 and 1560mg/kg ethanol. Ethanol doses of 1000mg/kg and greater produced more than 80% ethanol-lever selection. The rats were then trained to orally self-administer 10% weight/volume ethanol and tested to determine if self-administered oral ethanol would substitute for experimenter administered i.p. ethanol. A mean self-administered ethanol intake of 1114mg/kg (±156mg/kg) produced 83% ethanol-lever responding. Restricted access to 560 mg/kg of self-administered ethanol resulted in 33% i.p. ethanol-lever responding. Doses of 100 and 320mg/kg ethanol did not substitute for i.p. ethanol. These data show that orally self-administered ethanol can produce discriminative stimulus effects that are similar to i.p. experimenter-administered ethanol and that orally self-administered ethanol produces centrally-mediated discriminative stimulus effects. Behav Pharmacol 1998; 9:329–336 © 1998 Lippincott-Raven Publishers.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Although accumulating evidence suggests that serotonergic drugs are able to substitute for the ethanol (EtOH) cue in rats, it is still unclear which 5-HT receptor subtypes are responsible for this phenomenon, and whether these receptors are critically involved in the EtOH cue. In the present study, rats were trained to discriminate EtOH (1000 mg/kg, i.p., t-15min) from saline in a two-lever food-reinforced procedure, and it was investigated to which extent serotonergic compounds with a certain level of specificity for either 5-HT1B, 5-HT2Aor S-HT2Creceptors generalized to the EtOH cue. Subsequently, the involvement of these receptor subtypes was ascertained by the use of selected 5-HT receptor antagonists. The 5-HT1Breceptor agonist CP 94,253 (0.3—5 mg/kg, i.p.) and the mixed 5-HTIB/2Creceptor agonist mCPP (0.1–1 mg/kg, i.p.), but not the preferential 5-HT2Areceptor agonist DOl (0.3—1 mg/kg, i.p.), completely generalized to the EtOH cue. Complete generalization of the former two compounds coincided with a decrease in response rate. In antagonism studies, it was shown that the 5-HT1Breceptor antagonist GR 127935 (10 mg/kg, i.p.) completely blocked generalization of CP 94,253 to the EtOH cue, suggesting that stimulation of 5-HT1Breceptors produces discriminative stimulus effects which are similar to those of EtOH. GR 127935 (10 mg/kg, i.p.), as well as the mixed 5-HTIB/2creceptor antagonist metergoline (1 mg/ kg, i.p.), and the 5-HT2Creceptor antagonist SB 206,553 (1 mg/kg, i.p.) completely blocked generalization of mCPP to the EtOH cue. This suggests that 5-HTIBand 5-HT2Creceptors are required for the generalization of mCPP to the EtOH cue. The present findings indicate that activation of 5-HT1Band S-HT2c, but not of 5-HT2Areceptors, mimics the EtOH cue. However, the finding that neither metergoline, nor the 5-HT2Areceptor antagonist MDL 100,907 blocked the EtOH cue, suggests that these receptors play only a minor role in the discriminative stimulus effects of a moderately low dose of EtOH. Behav Pharmacol 1998; 9:337–343 1998 Lippincott-Raven Publishers.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

There is growing evidence of a functionally significant link between the perifornical region of the lateral hypothalamus (PFH) and the mesoaccumbens dopamine projection. The present study assessed the ability of intra-accumbens dopamine receptor blockade, firstly to impair the locomotor stimulant properties of intra-PFH sulpiride, and secondly the ability of intra-PFH sulpiride to support a conditioned place preference. Locomotor activity and conditioned place preference training were assessed using an apparatus consisting of three distinctive compartments. Following a pre-exposure session in which groups showed equivalent preference for the three compartments, conditioned place preference training was carried out over five drag (0, 0.03 or 0.1 jig Intra-accumbens sulpiride; 0 or 5üg intra-PFH sulpiride) and five vehicle sessions. For each animal, drug and vehicle treatments were randomly paired with one of the two outermost compartments. Locomotor activity was monitored during each session. Intra-PFH sulpiride alone increased locomotor activity during later sessions, and this gradual increase in locomotor response, relative to vehicle infusions, was blocked by intra-accumbens sulpiride co-infusion. On the final drug-free test day for conditioned place preference, animals were again permitted free access to all three compartments, and the time spent in each was compared with that on initial exposure. Intra-PFH sulpiride alone supported a conditioned place preference. Intra-accumbens sulpiride was without intrinsic effect, but nevertheless blocked the ability of intra-PFH sulpiride to support a conditioned place preference. These data provide further support for a functionally significant link between the PFH and mesoaccumbens dopamine projection, with regard to the locomotor stimulant properties and ability of intra-PFH infusions of sulpiride to support a conditioned place preference. Behav Phannacol 1998; 9:345–355 © 1998 Lippincott-Raven Publishers.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

We demonstrated previously that several parameters of a morphine discrimination were significantly different in female versus male rats, using a fixed ratio (FR)-l0 schedule of food reinforcement however, this schedule produced a significant bias in reinforcement frequency between saline and morphine sessions in males but not in females. To determine whether this schedule—drug—sex interaction caused the sex difference in discriminability of morphine, female and male rats were trained to discriminate 3.0mg/kg morphine from saline using a variable interval (VI) 15-s/VI 15-s(Phase 1), a VI 7.5-s/Vl 15-s(Phase II), and a VI 15-s/Vl 15-s(Phase 111) schedule of food reinforcement on morphine/saline levers, respectively. After a minimum of 40 training sessions in each phase, mean reinforcement rates in morphine sessions were highest and the ED50values for morphine discrimination were lowest, in Phase II. Thus, as predicted, the morphine dose-effect curves shifted to the left from Phase 1 to Phase II, and back to the right from Phase n to m, presumably due to the bias in reinforcement rate between saline and morphine sessions that was induced by manipulating the VI schedule on the morphine lever. However, there were no sex differences in the morphine versus saline reinforcement rate or in discrimination ED50in any phase, suggesting that the sex difference observed in our initial study was probably due to the bias in reinforcement frequency (towards the saline condition) that occurredonly in malesunder the FR-10 schedule. This study demonstrates the importance of considering group differences in schedule—drug interactions when comparing discriminative stimulus properties of drugs between groups. Behav Pharmacol 1998; 9:357–362 1998 Lippincott-Raven Publishers.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

This study proposes a method to assess voluntary alcohol drinking in socially living squirrel monkeys. Group-housed squirrel monkeys were induced to drink a sucrose solution and subsequently an etbanol/sucrose solution in an experimental chamber attached to the home colony room, allowing the daily intake to be monitored for each individual without disrupting the social context. Sucrose concentration (0.03–0.6 M, corresponding to 1–20%) and ethanol concentration (0–4%) were gradually increased in tap water and in a 0.6 M (ca. 20%) sucrose solution during daily 30-min and 10-min sessions, respectively. Blood ethanol levels ranged from 10–50 mg/dl and remained below intoxication level. These experiments demonstrate that it is feasible to arrange conditions under which individual socially housed squirrel monkeys voluntarily drink a sweetened ethanol solution. Behav Pharmacol 1998; 9:363–367 1998 Lippincott-Raven Publishers.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The additive effect of social and pharmacological treatments was evaluated in pairs of male mice. Ineffective and effective doses of morphine (2.5 and 5.0 mg/kg, i.p.) were tested on pain threshold in dyads of males at different times after pair formation and drug treatment. During the second hour of social interaction after reunion, saline-injected adult sibling male mice showed a decrease in nociception as measured by the tail-Hick test. Pairs of unrelated, unfamiliar control mice showed no changes in pain sensitivity during a 2-h social session. An ineffective dose of 2.5 mg/kg of morphine in nonsibling males, significantly increased tail-flick latencies in sibling pairs, before the effect of the social environment (sibling) reached statistical significance. The higher dose of morphine (5.0 mg/kg) produced analgesia in sibling as well as in nonsibling males, but the effect in the latter disappeared 60 min after drug treatment, whereas siblings were still analgesic. These results indicate that an ineffective dose of morphine, combined with the activation of the endogenous opioid system by social factors, can affect nociception. Behav Pharmacol 1998; 9:369–373 1998 Lippincott-Raven Publishers.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

A recent report suggested that barakol, a biologically active extract of the south-east Asian plant, Cassia siamea, has anxiolytic properties. The purpose of the present study was to replicate and extend these findings by examining the dose–response effects of barakol (0–20mg/kg) in two pharmacologically validated tests of rat anxiety: the elevated plus-maze and the shock-probe burying tests. Although the purity of our sample of barakol was confirmed by chemical analysis, we found no evidence of its anxiolytic effects in either the plus-maze or shock-probe burying tests. Behav Pharmacol 1998; 9:375–378© 1998 Lippincott-Raven Publishers.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID