摘要:

Administration of amphetamine (AMPH) can induce symptoms of psychosis in humans and locomotor sensitization in rats; in contrast, withdrawal from a period of AMPH intake is most often associated with symptoms of human endogenous depression. The aim of this study was to determine whether AMPH withdrawal produces a depressive-like state in rats.The present study examined the effects of withdrawal from an escalating-dose AMPH schedule (ESC; three daily injections over 6 days, 1–5 mg/kg, i.p.) and an intermittent-dose AMPH schedule (INT; one daily injection over 6 days, 1.5 mg/kg, i.p.) on animals' performance in three behavioral paradigms related to depression: the Porsolt swim test, the learned helplessness assay and operant responding for sucrose on a progressive ratio schedule.ESC and INT AMPH withdrawal had no effect on any of these tests or on stress responsiveness as measured by increased plasma levels of corticosterone (CORT) and adrenocorticotropin following the swim test, although basal CORT levels were higher in AMPH-withdrawn animals compared to controls. Finally, we confirmed the presence of locomotor sensitization for both AMPH schedules after 30 days of withdrawal.Our results suggest that the ability of AMPH withdrawal to produce symptoms of depression may not be evident in all behavioral screens for depressive symptoms in the rat.

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Based on previous animal work, the present study investigated whether individual differences in motor activity in a novel environment predicted reinforcing and behaviorally activating effects of D-amphetamine (0, 5, 10 and 20 mg p.o.) in healthy adults.When exposed to a novel environment, 18 participants had high levels of motor activity (high responders; HR) and six had low levels (low responders; LR). These group differences were used to predict effects of D-amphetamine on drug reinforcement, salivary cortisol, motor activity, subjective effects, and acoustic startle reflex in subsequent sessions.Unlike observations in rodents, (1) dose-dependent reinforcing effects of D-amphetamine were evident but without group differences; (2) motor activity was greater in HR but did not vary with D-amphetamine dose; and (3) cortisol levels were not related to the reinforcing effects of D-amphetamine. Startle reflex amplitudes were greater in HR following placebo, but D-amphetamine 20 mg equalized this group difference. There was a trend towards less prepulse inhibition of the acoustic startle reflex in HR compared to LR. LR reported greater overall negative effect following amphetamine administration, but this was not consistently related to dose. Finally, participants with high sensation-seeking personality scores exhibited less prepulse inhibition. The results are discussed in terms of the extant literature.

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Lever pressing in rats (N=5) was reinforced under a progressive-ratio (PR) schedule of food presentation, in which the number of responses required increased exponentially. The session was terminated when 1 h passed without completion of the scheduled ratio. Doses of cocaine (5.6–42.0 mg/kg; one subject received a dose of 56.0 mg/kg) as well as saline were administered i.p. prior to the session.Under non-drug conditions, breakpoints were typically less than 100, and substantial responding usually occurred only during about the first 10 min of the session. The rate of responding usually increased over the first 2–8 reinforcers and then decreased for the last few reinforcers obtained. For four of five rats, breakpoint, overall rate of response, and session duration were first increased above control and vehicle levels by increasing doses of cocaine. Larger doses produced smaller increases, no effect, or decreases. Cocaine, in the range of doses near the apex of the breakpoint dose–effect functions, suppressed rates of responding at the small ratios present at the beginning of the session.It is suggested that cocaine increases low rates of response if: (1) rates are low due to extinction; and (2) the stimuli present are those present when the response is reinforced.

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The interactions of&agr;2-adrenoceptors and acute restraint stress with morphine state-dependent memory of passive avoidance were examined in mice. Memory acquired following pre-training morphine administration (5 mg/kg, i.p.) was dose- and time-dependently retrieved by pre-test morphine; this effect was reversible by yohimbine (1 mg/kg). Pre-test clonidine (0.005–0.1 mg/kg) was also effective in restoring morphine-induced memory. Pre-training clonidine (2 mg/kg) induced an amnestic effect that was restorable by pre-test clonidine or morphine; this effect was also blocked by yohimbine. Acute pre-training stress for 2 h induced an amnestic effect that was reversible by pre-test morphine (1 and 5 mg/kg) or clonidine (0.01 and 0.1 mg/kg). Finally, acute pre-test stress could restore the impairment of memory induced by pre-training morphine. The data are suggestive of a functional interaction betweenμ-opioid,&agr;2-adrenergic receptors and stress in modulating state-dependent learning and memory.

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

It is well known that neuroleptic-induced catalepsy in rats intensifies upon repeated testing. Here, the question is addressed whether intensification of catalepsy results from intermittent drug administration or from intermittent context exposure.In experiment 1, rats were treated with intermittent haloperidol injections (0.25 mg/kg) followed by the catalepsy test (descent latency from the horizontal bar). In experiment 2, rats were lesioned with 6-hydroxydopamine injections into the striatum, resulting in a 45% reduction of dopamine concentration. Catalepsy was tested intermittently for several weeks. In both experiments we found a very stable intensification of catalepsy over 9 (haloperidol rats) and 11 (lesioned rats) days, showing that intensification is not due to intermittent dopamine depletion. In both experiments, intensification of catalepsy was very stable and was observed 18 days later in haloperidol-treated rats and 101 days later in lesioned animals. However, a change of the environmental context abolished the intensified catalepsy in both experiments.It is concluded that intensification of catalepsy is due to intermittent context exposure rather than intermittent drug administration. It is generally accepted that 6-hydroxydopamine lesions represent an animal model of Parkinson's disease. Given the results above, context-dependent intensification of parkinsonian symptoms might also occur in Parkinson's disease, and its prevention should be taken into consideration for future therapy of the disease.

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

It was shown previously that effects of drugs present prior to training sessions could serve as discriminative stimuli. Further experiments have aimed to determine whether a second drug can serve as a mediating stimulus that increases the strength of stimulus control by such pre-session drug effects.Rats were trained in a two-lever discrimination procedure with food reinforcers presented on a tandem variable-interval fixed-ratio (VI-FR) schedule. Injections of nicotine (0.6 mg/kg) or saline were followed after 5 min by administration of midazolam (0.2 mg/kg) as a putative mediating stimulus. The nicotine antagonist mecamylamine (1.0 mg/kg) was administered 5 min after midazolam, to block effects of nicotine during training sessions, as in previous work on pre-session drug effects.Stimulus control was acquired slowly and to an accuracy of only 75%. Midazolam did not facilitate the acquisition or magnitude of nicotine-induced stimulus control. However, extinction tests showed that the presence of midazolam was required for expression of stimulus control by pre-session effects of the training dose of nicotine. The response to nicotine (0.075–0.6 mg/kg) was dose-related, but the dose–response relationship was not dependent upon the presence of midazolam. In a group of rats trained with nicotine and midazolam as above, but without mecamylamine, stimulus control by nicotine was not dependent upon the presence of midazolam. In all cases, overall rates of responding were very low when tests were carried out without midazolam, suggesting the presence of state-dependent learning.The results imply that under appropriate conditions the discriminative stimulus effects of one drug (nicotine) can be mediated by the action of a second substance (midazolam). This finding can be conceptualized in terms of occasion setting, with nicotine serving as the feature and midazolam as the target stimulus. Furthermore, it appears that even when rates of responding show drug-state dependence, this is not necessarily the case for discriminative stimulus effects.

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The purpose of this study was to determine the effects of the benzodiazepines, midazolam and chlordiazepoxide, and the barbiturate, pentobarbital, on spatial learning, in a within-subject, repeated-acquisition and performance procedure adapted to the Morris Swim Task.In the presence of one stimulus arrangement, rats learned to swim to a hidden escape platform that was always in the same location in a swimming pool (performance component). In the presence of a second stimulus arrangement, the platform moved to a different place in the pool for each daily session (acquisition component). All subjects completed six training trials in both components during each daily training session, alternating between the two components within each session.Relatively direct paths to the platform and short escape latencies in the performance component, and steep within-session learning curves in the acquisition component, demonstrated that behavior under each component was controlled by the discriminative stimuli. All three GABAAmodulators increased swim distances, escape latencies, and slowed swim speed in a dose-dependent manner. Midazolam and chlordiazepoxide, but not pentobarbital, produced selective impairments of swim distances and escape latencies in the acquisition component. Benzodiazepines disrupted acquisition at doses that did not disrupt steady-state performance. Pentobarbital impaired acquisition only at doses that also disrupted behavior during the performance component and reduced swimming speeds.

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The present study examined the influence of sex on the antinociceptive effects of (−)-pentazocine, morphine and spiradoline in four rat strains, using a warm-water (50, 52 and 55°C) tail-withdrawal procedure.In F344, Lewis, Sprague–Dawley (SD) and Wistar rats, baseline latencies decreased with increases in water temperature, and at each water temperature latencies were longer in males than in their female counterparts. Morphine and spiradoline produced maximal or near maximal antinociceptive effects in males and females of each strain. Whereas morphine was generally more potent in males, sex differences were not consistently observed with spiradoline. In contrast, there were marked sex differences with (−)-pentazocine, and in each strain (−)-pentazocine was more potent and produced a greater maximal effect in males. The magnitude of the sex differences varied markedly across strains, with (−)-pentazocine being 2.5-fold more potent in males of the F344 strain, but 11-fold more potent in males of the Wistar strain. When collapsed across nociceptive stimulus intensities, sex differences were largest in the Wistar and Lewis strains and smallest in the SD and F344 strains.The present findings indicate that there are marked sex differences in (−)-pentazocine antinociception, and that the magnitude of this effect is genotype dependent.

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Recent clinical evidence supports the potential of neurokinin NK1 receptor antagonists as novel antidepressant drugs. A number of NK1 antagonists have reduced affinity for rat and mouse NK1 receptors compared to human, making it difficult to test for efficacy in traditional animal models. NK1 antagonists, in general, have similar affinity at gerbil and human NK1 receptors. The aims of these studies were, first, to validate the gerbil tail suspension test, a test used frequently to demonstrate antidepressant drug efficacy in mice, and second, to determine whether the test could be used to demonstrate the antidepressant potential of NK1 antagonists.Immobility time was reduced by oral administration of the antidepressants imipramine (3–30 mg/kg), desipramine (1–30 mg/kg), amitriptyline (30 mg/kg), fluoxetine (1–30 mg/kg), paroxetine (3–10 mg/kg), citalopram (0.1–3 mg/kg), sertraline (1–30 mg/kg), venlafaxine (1–30 mg/kg) and nefazodone (100 mg/kg). Furthermore, oral administration of the NK1 antagonists MK-869 (10 mg/kg), L-742,694 (10 mg/kg), L-733,060 (10 mg/kg), CP-99,994 (30 mg/kg), and CP-122,721 (3–30 mg/kg) reduced immobility time. Diazepam (1–10 mg/kg), chlordiazepoxide (1–10 mg/kg), buspirone (3–30 mg/kg), FG-7142 (1–30 mg/kg), and haloperidol (1–10 mg/kg) did not reduce immobility. Amphetamine (0.3–10 mg/kg) and atropine (0.3–10 mg/kg) reduced immobility, suggesting susceptibility to false positives, e.g. compounds that affect locomotion. Compounds were therefore tested in a gerbil locomotor activity (LMA) test to ensure that the antidepressant-like effects were not secondary to effects on activity. Antidepressant drugs and NK1 antagonists had no effect on LMA at doses that reduced immobility, whereas amphetamine and atropine induced marked hyperactivity.These studies support both the utility of gerbils in behavioral pharmacology and the antidepressant potential of selective NK1 antagonists.

ISSN:0955-8810    

出版商:OVID    

年代:2003

数据来源: OVID