ISSN:0955-8810    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Rats were trained to detect the stimulus properties of fentanyl, 0.04mg/kg. Tested acutely, fentanyl generalized to, and morphine substituted for, the fentanyl training stimulus, although morphine was approximately 100-fold less potent than fentanyl in producing this stimulus. Subsequently, these rats were implanted with pumps (0.25ml volume) that delivered osmotically 1μl/h of solution containing either 3μg/μl (n= 16) or 6μg/μl (n= 16) of fentanyl. When tested shortly after pump implantation, saline administration resulted in fentanyl-lever selection, indicating that the pumps were releasing fentanyl. Fentanyl-lever selection peaked at approximately 8h after implantation; by 24 to 72h after implantation, saline injection produced mainly saline-lever selection. On days 4 and 5 of chronic infusion of fentanyl, the fentanyl and morphine dose-effect curves were redetermined in both groups: both curves had shifted upwards, and the degree of shift occurred as a function of the dose of fentanyl infused continuously. After 6 days of infusion, the pumps were removed, and the detection of the fentanyl training stimulus was tested at 4, 12 and 24h after pump removal. At 12h after removal, the percentage of subjects selecting the fentanyl lever following 0.04mg/kg of fentanyl decreased to 53%, and this recovered to 87% by 24h following pump removal. These results demonstrate tolerance to the stimulus properties of opioids with a few hours from the time of insertion of the pumps; the tolerance was not complete as shown by the results obtained during dose-effect testing with the pumps in place; finally tolerance was observed for a brief period when the pumps infusing fentanyl were removed (withdrawal tolerance). No evidence was obtained for asymmetric tolerance between fentanyl and morphine.

ISSN:0955-8810    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The present experiments further characterized intravenous self-administration of the short-acting benzodiazepine midazolam in rats under conditions of unlimited access to the drug. The results of the first experiment demonstrated that rats responded at higher rates on a lever that produced an infusion of 0.05mg midazolam than on a lever that did not result in reinforcement, and that they transferred responding to the other lever when the reinforcement contingencies were reversed. These results provide further evidence of the reinforcing effects of midazolam. In the second experiment, rats responding at stable rates for 0.05mg midazolam per infusion exhibited increased responding when transferred to a lower dose (0.0125mg/infusion) and decreased responding when transferred to a higher dose (0.20mg/infusion) of the drug. However, the inverse relationship between responding and drug dose was apparent only during the first transfer session, after which no consistent relationship was observed. In support of previous observations, all rats exhibited a temporal pattern of responding for midazolam over the 24h sessions, with maximal responding occurring during the dark phase of the 12h light/dark cycle. However, the present results also provide preliminary evidence that rats given prolonged access to midazolam (more than 49 days) develop a more constant within session pattern of responding for midazolam. This may be related to the development of physical dependence and reflect an attempt to avoid withdrawal effects by maintaining a stable intake of midazolam within a session.

ISSN:0955-8810    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Many drugs produce compound discriminative stimuli with at least two elements; in contrast, the present study examines discrimination of a mixture of two drugs and tests the role of training dose in, and the specificity of, such a discrimination. Rats discriminated a mixture of nicotine (0.2mg/kg s.c.) and midazolam (0.1mg/kg s.c.) from saline in a two-bar operant conditioning procedure with accuracy of at least 80%. Stimulus control was analyzed by testing each drug separately. Initially, stimulus control was mainly attributable to the midazolam. The doses of drugs used to maintain the discrimination were then altered. As the training dose of nicotine increased and that of midazolam decreased, the magnitudes of responses to the separate drugs were progressively reversed, until stimulus control was mainly attributable to nicotine. Thus, responses to the components of the compound stimulus were systematically related to the amounts of drugs in the mixtures used to maintain the discrimination, and there was some evidence that a strong stimulus produced by one drug may have overshadowed a weaker stimulus produced by a different agent. To test specificity, generalization to other drugs was examined. There was no generalization to amphetamine, morphine or quipazine, up to doses that reduced overall rates of responding. It follows that cues produced by mixtures of drugs may be as specific as those produced by single agents.

ISSN:0955-8810    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Effects of ipsapirone on rats were studied in procedures in which tolerance was assessed with operant responding and in feeding tests. Initially, the suppressant effect of ipsapirone on Fixed Ratio 20 behaviour was studied. During 33 days treatment (7.5mg/kg daily) no tolerance developed. Subsequently, the same rats received ipsapirone (7.5mg/kg) three times daily, at intervals of 2.5h, the first injection preceding operant sessions. Over 10 further days of treatment, there was still no evidence of tolerance. In a second study, ipsapirone was again administered at 7.5mg/kg before operant sessions, followed by 2 daily injections of 20mg/kg, at at 2.5h intervals after operant sessions. Under these conditions,sometolerance developed although it was incomplete and rapidly lost. The effects of ipsapirone on operant responding were found to be short-lasting. The suppressant action of 7.5mg/kg of ipsapirone (to 50% of baseline) was abolished if the drug was injected 4h before sessions. In other studies, we confirmed that tolerance develops very rapidly to hyperphagic actions of ipsapirone (see Kennettet al., 1987). We conclude that: 1) tolerance develops at differing rates to various effects of ipsapirone; 2) only those effects of ipsapirone (and related agents) which involve activation of presynaptic autoreceptors show rapid tolerance; 3) tolerance develops to effects on operant responding only if high doses are administered frequently. Since ipsapirone is short-acting, tolerance to such effects develops only when drug is continuously present in body tissue. The tolerance observed (to effects on operant behaviour) was probably of a pharmacodynamic nature and did not involve learning processes.

ISSN:0955-8810    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Effects of the benzodiazepine receptor antagonist ZK 93 426 were examined in two groups of rats with long lasting radial maze impairments caused by either ibotenic acid lesions to cholinergic forebrain projections or 28 weeks of alcohol treatment. Animals were trained on the 8-arm radial maze prior to ibotenic acid treatment or following chronic alcohol treatment. Spatial and associative working and reference memory were investigated in parallel. Lesioned rats showed high error rates in all aspects of memory, but particularly in spatial working memory, whilst error rates in alcohol-treated rats were low and uniform.ZK 93 426 improved performance in both experiments. In lesioned rats working memory errors were selectively decreased, in line with evidence that ZK 93 426 enhances attention. However in alcohol-treated rats both reference and working memory errors were reduced to control level, suggesting that these animals primarily showed a mild attentional deficit.Alcohol treatment and lesions were both found to reduce cortical choline acetyltransferase activity, but in view of the non-specificity of alcohol or ibotenic acid to cholinergic neurons and the wide distribution of the GABA-BZ receptor complex, interactions of ZK 93 426 with other systems cannot be ruled out.

ISSN:0955-8810    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

White Carneau pigeons were trained to discriminate 1.0 mg/kg buspirone from saline when key pecking was maintained under a fixed-ratio 30 schedule of food presentation. Buspirone (0.3–10.0 mg/kg), the serotonin 1A (5-HT1A) agonist 8-OH-DPAT (0.1–1.0mg/kg), the buspirone analog BMY 7378 (3.0–5.6mg/kg), the mixed 5-HT1A/1Bagonist RU 24969 (3.0–10.0mg/kg) and the 5-HT1Aagonist spiroxatrine (0.1–1.0mg/kg) occasioned at least 80% buspirone-appropriate responding in all subjects tested. Administration of the 5-HT1Bagonist (TFMPP 0.1–10.0mg/kg) or the 5-HT3antagonist (MDL 72222 (3.0–17.0mg/kg) resulted in primarily saline-key responding. The dopamine receptor antagonist chlorpromazine (1.0–17.0mg/kg), the specific D-2 receptor antagonist eticlopride (0.03–0.56mg/kg), the noradrenergic alpha-2 antagonist yohimbine (0.1–1.0mg/kg), the alpha-2 agonist clonidine (0.003–0.10mg/kg) and (±) and (-) propranolol (3.0–30.0mg/kg) all produced primarily saline-appropriate responding. Coadministration of the β-adrenergic agonist isoproterenol (1.0–5.6mg/kg) or the 5-HT1Apartial agonist BMY 7378 (0.01–10.0mg/kg) with 1.0mg/kg buspirone did not block the discriminative stimulus effects of buspirone. However, 3.0–10.0mg/kg BMY 7378, in combination with a lower dose of buspirone (0.3mg/kg) decreased drug-key responding to approximately 50%. Results from the present study suggest that (1) the discriminative stimulus effects of buspirone, 8-OH-DPAT, BMY 7378, RU 24969 and spiroxatrine are mediated through the 5-HT1Areceptor; (2) buspirone's discriminative stimulus effects do not interact with the noradrenergic or dopaminergic system; and 3) under this procedure BMY 7378 was a partial agonist at 5-HT1Areceptors.

ISSN:0955-8810    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The effect of antidepressant drugs (ADs) on the rewarding properties of food, given to food-deprived rats, was studied with a conditioned place preference paradigm. Repeated (once a day for 4 days) association of an initially non-preferred environment with the presentation of food resulted in development of an increased preference for that environment. That effect was diminished when each conditioning session was preceded by administration of single doses of imipramine, desipramine, amitriptyline, mianserin and citalopram (short-term treatment). In contrast, long-term treatment (16 days) with the above ADs, as well as repeated (9) applications of electroconvulsive shock significantly enhanced the food-induced place preference conditioning. In a separate experiment it was also found that ADs, used as unconditioned stimuli, produced a conditioned aversion to the environment previously paired with administration of single doses of the drugs. The above findings are discussed in terms of the enhancement by prolonged antidepressant treatments of the brain reward mechanisms.

ISSN:0955-8810    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Behavioural and pharmacological evidence suggest that non-opioid analgesia in defeated male mice is a consequence of anxiety provoked by ecologically relevant aspects of the stimulus situation. The effects of acute and chronic alprazolam (0.05–2.0mg/kg, i.p.) treatment on basal nociception, defeat behaviour and analgesia evoked by conspecific attack are assessed. Results show that basal nociception (tail-flick assay) was unaffected by acute or chronic drug treatment, and that attack-induced analgesia was unaltered by acute administration of 0.05–0.50mg/kg alprazolam. Higher acute doses (1–2mg/kg) of the compound inhibited locomotor activity, markedly interfered with the display of defeat postures and resulted in the exposure of intruders to higher than normal levels of attack. Though 1mg/kg alprazolam (acute) significantly inhibited the analgesic consequences of conspecific attack, this effect went at a higher dose. Chronic drug administration led to the development of tolerance to the inhibitory effects of higher alprazolam doses on locomotor activity and, over the dose range 0.5–2mg/kg, to the complete inhibition of analgesic consequences of conspecific attack. Nonetheless, mice treated chronically with 0.5–2mg/kg still failed to display defeat within the maximum time allotted for encounters, suggesting that this behavioural effect may be a valid index of anxiolytic activity. Data are discussed in relation to the possible involvement of panic in intruder analgesia.

ISSN:0955-8810    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Pair-housed, water-deprived rats were trained to run in a two-way shuttle box, using water reinforcement. Animals were tested either singly or in pairs; in the paired condition, the animals were required to shuttle in close physical proximity. Paired performance, but not single performance was severely disrupted by single housing for 3–7 weeks. Performance of singly-housed animals could be restored either by re-housing in pairs (30 days) or by chronic (30 day) treatment with the antidepressants imipramine or fluoxetine. Chronic imipramine was also prophylactically active in preventing the deterioration in performance of singly-housed animals.The superior paired performance of pair-housed animals and of imipramine-treated singly-housed animals, was abolished by the 5-HT antagonist metergoline. Metergoline had relatively little effect on single running; the DA antagonist pimozide disrupted paired and single running equally. The results suggest a role for 5-HT in cooperative performance and in the action of antidepressant drugs in this paradigm.

ISSN:0955-8810    

出版商:OVID    

年代:1989

数据来源: OVID