摘要:

The unconditioned behavioural effects of two non-peptide δ-opioid receptor agonists, BW 373U86 and SNC 80, were studied in the intact rat. BW 373U86 (0.1–2.5 mg/kg s.c.) and SNC 80 (2.5–10 mg/kg s.c.) dose-dependently elicited locomotion, rearing, stereotyped sniffing, licking and gnawing. These effects were abolished by pretreatment with the δ-opioid receptor antagonist naltrindole (5.0 mg/kg s.c.). In view of the phenomenological similarities between this syndrome and that elicited by dopamine-receptor agonists, the role played by dopamine receptors was investigated. The specific dopamine D1receptor antagonist SCH 23390 and the specific dopamine D2/D3receptor antagonist raclopride reduced or even abolished the behavioural stimulation induced by lower doses of BW 373U86 and SNC 80. When higher doses of BW 373U86 were used (2.5 mg/kg), however, raclopride, even at high cataleptic doses (6.0 mg/kg), only partly prevented the behavioural stimulation induced by the δ-opioid receptor agonist. The behavioural stimulation remaining after high doses of raclopride was abolished by the administration of SCH 23390. These results show that δ-opioid receptor stimulation elicits dopamine-dependent behavioural activation in the rat that depends on dopamine receptors, particularly of the D1subtype.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The motivational properties of the non-peptide δ-opioid receptor agonists BW373U86 and SNC 80 were investigated using the place-conditioning paradigm. BW373U86 (0.5–1.0 mg/kg s.c.) and SNC 80 (1.25–5.0 mg/kg s.c.) elicited significant preference for the drug-paired compartment, in a dose-related fashion. Naltrindole (5.0 mg/kg s.c.) pretreatment, while failing to modify preference when given alone, completely prevented place-preference induced by BW373U86 (1.0 mg/kg s.c.) and SNC 80 (1.25 mg/kg s.c.). The dopamine D1receptor antagonist SCH23390, given at doses that do not affect place-preference (0.012 mg/kg s.c.), completely prevented the place-preference induced by BW373U86 and SNC 80. At the doses effective in eliciting place-preference, BW373U86 and SNC 80 failed to modify extracellular dopamine in the medial nucleus accumbens, while in the dorso-lateral caudate-putamen BW373U86 (1.0 and 2.5 mg/kg s.c.) reduced extracellular dopamine, and this effect was prevented by naltrindole (5.0 mg/kg s.c.). SNC 80, only at the dose of 5 mg/kg s.c., significantly reduced extracellular DA in the dorso-lateral caudate-putamen. The results indicate that stimulation of δ-opioid receptors has incentive properties that might be related to an indirect amplification of post-synaptic dopamine transmission.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

In unilaterally 6-hydroxydopamine lesioned rats the ability of two non-peptide δ-opioid agonists, BW 373U86 and SNC 80, to induce motor asymmetries, alone or in combination with low doses of specific D1or D2agonists, was investigated. BW 373U86 and SNC 80 failed to induce motor asymmetries by themselves, but elicited contralateral turning after pretreatment with a dose of SKF 38393, a D1agonist, or quinpirole, a D2agonist, whichper sedid not induce contralateral turning. BW 373U86 also potentiated contralateral turning induced by threshold doses of quinpirole. Facilitation of D1-dependent contralateral turning was associated with a potentiation of c-fos expression, as estimated by Fos-like immunoreactivity, in the dorsal caudate-putamen, particularly in its lateral aspect. Potentiation of D2-dependent contralateral turning was associated with a reduction of c-fos expression in the medial caudate-putamen. It is concluded that stimulation of δ-opioid receptors facilitates the expression of D1and D2responses arising from the denervated striatum.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Prepulse inhibition (PPI) of the acoustic startle response is a behavioural tool used to assess sensorimotor gating processes and its disturbances in rats and in humans. PPI in rats is reduced by an overactivity of the dopamine (DA) system. Because there are functional interactions between DA and adenosine receptors, we tested whether PPI can be influenced by the mixed DA receptor agonist apomorphine (APO) and by the unselective adenosine antagonist theophylline (THEO). Combined administration of APO (0.5 mg/kg, i.p.) and THEO (20 mg/kg, i.p.) in doses devoid of significant effects on their own significantly reduced PPI. The PPI-disrupting effect of the combined THEO plus APO treatment was dose-dependently antagonized by co-administration of the selective adenosine A1agonist CPA (0.15–1.5 mg/kg, i.p.), but not by the A2Aagonist CGS21680 (0.1–2 mg/kg, i.p.). These data demonstrate that antagonistic interactions between DA and adenosine, involving adenosine A1receptors, play an important role in the regulation of PPI. The possible implications of these findings for the use of adenosine agonists in the treatment of schizophrenia are discussed.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

When ethanol is used as a training stimulus in drug discrimination experiments, benzodiazepines (such as diazepam) as well as non-competitiveN-methyl-D-aspartate (NMDA) antagonists (such as ketamine) substitute for ethanol; in contrast, when a benzodiazepine or an NMDA antagonist is used as a training drug, ethanol does not substitute reliably. In the present experiments, we trained rats to discriminate a mixture of diazepam and ketamine, to test the hypothesis that ethanol would substitute for this drug combination. Using a two-lever choice procedure with food as a reinforcer, 22 rats were trained to discriminate a mixture of diazepam (5.6 mg/kg) and ketamine (10 mg/kg) from vehicle. When administered as a mixture, diazepam and ketamine substituted for the training mixture in a dose-dependent manner. When administered separately, diazepam or ketamine substituted for the mixture with full substitution occurring at 5.6 and 17.8 mg/kg, respectively. Ethanol almost completely substituted for the mixture at 1 g/kg. There was no cross-substitution between diazepam and ketamine in rats trained to discriminate diazepam (5.6 mg/kg,n= 10) or ketamine (10 mg/kg,n= 12) from vehicle. In addition, ethanol did not substitute for the training drug in either of these discriminations. These results suggest that the simultaneous action of GABAAagonist and NMDA antagonist mechanisms produce a greater ethanol-specific discriminative stimulus than activation of either component individually.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

In order to study the dynamics of ethanol drinking behaviour, male Wistar rats were given the free choice between tap water, and 5, 10 and 20% ethanol solutions. After 8 weeks of continuous access, the animals were repeatedly deprived of the ethanol solutions for 3 days every 4 weeks. In the first experiment, drinking patterns were recorded for 24 h with an electronic drinkometer device, at different time-points of ethanol experience and after an ethanol deprivation episode. The preference for more highly concentrated ethanol solutions as well as ethanol consumption increased with continuing ethanol experience. Furthermore, after the ethanol deprivation episode, the animals immediately and preferentially drank from the 20% ethanol solution, the most highly concentrated ethanol solution offered. Additionally, the number of drinking bouts, particularly at the 10 and 20% ethanol solutions, was increased during the first hour after ethanol re-presentation. In a second experiment, the effects of repeated ethanol deprivation experience, inherent in this self-administration paradigm, on anxiety-related behaviour were tested on the elevated plus-maze. Repeated ethanol deprivation proved to be more anxiogenic than the first deprivation experience. Taken together, these findings suggest that ethanol deprivation is anxiogenic in long-term voluntarily ethanol-drinking rats, which is increased by repeated ethanol deprivation experience. The possibility that anxiety during ethanol deprivation might contribute to the ‘relapse’-like drinking behaviour is discussed.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

A reduced behavioral sensitivity to drugs acting on central GABAergic, serotonergic, opioid and cholinergic systems has previously been identified in predominantly male malnourished animals. The present study sought to compare the effects of the non-competitiveN-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on responding maintained by a differential reinforcement of low rates (DRL-18s) operant schedule in two groups of rats with different prenatal nutritional histories (well-nourished and protein restricted). The schedule required that the rats space their responses at least 18 s apart in order to obtain food reinforcement (timing behavior). After training to a stable high proficiency, MK-801 was administered to female rats (Experiment 1) at doses of 0 (saline), 0.004, 0.008, 0.016, 0.024 or 0.032 mg/kg (doses expressed as the free-base). MK-801 produced dose-dependent decreases in the percentage efficiency of responding and the number of rewarded responses, with dose-dependent increases in the number of responses emitted. Prenatal malnutrition significantly shifted the inter-response time (IRT) curve to the left, relative to that of the well-nourished controls, leading to a significantly lower efficiency and a lower number of reinforcers, at an MK-801 dose of 0.016 mg/kg. In Experiment 2, the effect of MK-801 on DRL performance was compared between male and female rats after prenatal malnutrition. In general, females proved more sensitive to MK-801 than males. Consistent with Experiment 1, a significantly greater drug impairment was observed in prenatally malnourished females compared with well-nourished females, albeit at a slightly higher dose (0.032 mg/kg). Prenatal malnutrition did not alter the drug response in male rats. These findings suggest that the behavioral response to NMDA blockade is augmented in adult female, but not male, rats after prenatal malnutrition.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

N-methyl-D-aspartate (NMDA) receptor blockade is thought to prevent the development of cocaine-induced sensitization. Moreover, when cocaine is administered daily along with dizocilpine infusion to previously sensitized rats, the extinction of sensitization occurs. We report here two sets of experiments: (1) Rats were infused with dizocilpine through a subcutaneous mini-pump (0.1 mg/kg/day) during the induction of cocaine sensitization and, after 2 or 7 days of wash-out, were challenged with: cocaine, dizocilpine plus cocaine or 3-((±)2-carboxypiperazin-4-yl)-propyl-L-phosphonic acid (CPP) plus cocaine. Cocaine induced stereotypy scores significantly lower than that produced by the two drug combinations. Animals infused with dizocilpine alone did not present stereotypies when challenged either with dizocilpine or with dizocilpine plus cocaine. (2) Rats previously sensitized to cocaine received dizocilpine by infusion and daily cocaine treatments for a week. During the first days of infusion, sensitization appeared to be significantly decreased, but it resumed the initial intensity on days 6–7. After 2 and 9 days of wash-out, the expression of sensitization could be retrieved only by dizocilpine plus cocaine. Two distinct forms of sensitization to cocaine thus seem to exist: one dependent on and the second independent of NMDA receptor activity.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Previous studies have indicated that dopamine D1receptors in the ventral tegmental area (VTA) may play an important role in the development of sensitization to amphetamine. The present study was designed to determine if D1receptors are also important in the development of cocaine-induced behavioral and neurochemical sensitization. Animals received intra-VTA injections of saline or the dopamine D1receptor antagonist SCH 23390 (15 nmol/side) 5 min before receiving systemic injections of saline or cocaine (15 mg/kg) on 4 consecutive days. One week later animals were challenged with cocaine. Motor activity and extracellular dopamine concentrations in the nucleus accumbens were monitored on the day the animals received the first of their four daily treatments and/or on the day animals received their cocaine challenge injection. Intra-VTA SCH 23390 attenuated the acute response, but did not alter development of the sensitized motor-stimulant response to cocaine. In contrast to the behavioral data, intra-VTA SCH 23390 blocked both the acute cocaine-induced increase in extracellular dopamine in the nucleus accumbens and development of the sensitized response. These data provide partial support for the role of dopamine D1receptors in the VTA in the development of cocaine-induced sensitization. The data also suggest, however, that additional mechanisms may play a role in the development of sensitization.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Cholestasis liver disease is associated with clinical and experimental findings consistent with increased opioidergic neuromodulation, increased plasma total activity, and elevated plasma enkephalin concentrations. The effect of the nitric oxide (NO) synthase inhibitor, L-nitro-arginine (L-NA, 0.03, 0.1, 0.3, 1 mg/kg), and the nitric oxide precursor, L-Arg (30 mg/kg), on antinociception induced by bile duct resection or sham operation, as well as on opioid dependence, was examined in male albino Swiss mice. Repeated (5 days) administration of L-NA attenuated signs of dependence, as assessed by naloxone (5 mg/kg)-precipitated withdrawal, and decreased the antinociception; however, L-Arg potentiated withdrawal signs and increased the antinociception. The results of this study support the involvement of the L-arginine/nitric oxide pathway in the opioidergic-dependent manifestation of cholestasis in an animal model.

ISSN:0955-8810    

出版商:OVID    

年代:1998

数据来源: OVID