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1.
Pre-exposure of rats to amphetamine sensitizes self-administration of this drug under a progressive ratio schedule 总被引:10,自引:8,他引:2
Two groups of male rats were tested to determine whether pre-exposure to d-amphetamine would enhance the motivation to self-administer the drug under a progressive ratio schedule of reinforcement.
In the first phase of the experiment, one group of rats received d-amphetamine (2 mg/kg IP), while a second group received saline on alternate days for a total of ten injections. Following
a 21-day drug withdrawal period, behavioral sensitization was confirmed by a significant increase in amphetamine-induced stereotypy
in the d-amphetamine-pretreated group, relative to the saline-pretreated group. In the second phase of the study, all rats were implanted
with chronic jugular catheters and trained to self-administer d-amphetamine (0.2 mg/kg per infusion) under a fixed-ratio schedule of reinforcement. The progressive ratio paradigm was then
imposed for 7 consecutive days; d-amphetamine-pretreated rats attained significantly higher break points than saline-pretreated animals. These data suggest
that pre-exposure to d-amphetamine may enhance the motivation to self-administer this drug.
Received: 16 July 1997 / Final version: 22 October 1997 相似文献
2.
We have established a rat model that reflects the course of development of alcohol and opiate addiction. The present study
with d-amphetamine aimed to define general principles in the development of an addiction. Male rats had a continuous free choice
between d-amphetamine solutions (100, 200 and 400 mg/l) and water for 47 weeks. An initial intake of high doses of d-amphetamine during the first weeks of drug choice was followed by an individually stable pattern of drug consumption of moderate
drug doses. During this period of controlled consumption (from week 10 to week 40), the voluntary intake of d-amphetamine depended on individual factors (dominant rats: 0.37 ± 0.02 mg/kg per day, subordinate rats: 0.57 ± 0.05 mg/kg
per day) and environmental variables (group housing: 0.21 ± 0.02 mg/kg per day, single housing: 0.41 ± 0.03 mg/kg per day).
Beginning with week 41, voluntary d-amphetamine consumption progressively increased (1.9 ± 0.2 mg/kg per day in week 47), although the experimental conditions
remained unchanged. Drug intake during a retest (free choice as before) after 6 months of drug deprivation revealed that the
rats had persistently lost their control over drug intake and were no longer able to adjust drug taking to internal and external
conditions. These addicted rats took very high drug doses, even when all d-amphetamine solutions but not water were adulterated with bitter tasting quinine (6.6 ± 0.6 mg/kg per day; age-matched controls:
0.37 ± 0.04 mg/kg per day). Forced intake of d-amphetamine for 47 weeks (7.1 ± 0.3 mg/kg per day) via the drinking fluid caused physical dependence (hyperreactivity during
withdrawal) but did not lead to drug addiction (voluntary intake in the retest with adulteration: 0.42 ± 0.04 mg/kg per day).
Both the temporal development and the prerequisites of psychostimulant addiction were in principle the same as for alcohol
and opiates.
Received: 3 April 1998/Final version: 26 August 1998 相似文献
3.
This study investigated the effects of repeated nicotine treatment on locomotor activity and behavioral inhibition, and the
influence of citalopram on the behavioral effects obtained. Male rats received daily subcutaneous injections of vehicle + vehicle
(veh + veh), citalopram (5.0 mg/kg) + vehicle (cit + veh), vehicle + nicotine (1.0 mg/kg; veh + nic) or citalopram+nicotine
(cit + nic). Acutely, nicotine stimulated locomotor activity, and repeated daily nicotine injections sensitized veh+nic rats
to the nicotine-induced locomotor stimulation after 5, 10 and 15 treatment days, whereas in cit+nic rats, the enhancement
of nicotine-induced locomotion was suppressed. However, when challenged with nicotine after citalopram withdrawal (−36 h),
the cit + nic treated animals were also observed to be sensitized. In the elevated plus-maze, repeated nicotine treatment
produced behavioral disinhibition, measured as an increase of time spent in and entries made into open arms (%), and chronic
citalopram treatment attenuated the expression of behavioral disinhibition. Moreover, the degree of nicotine sensitization
correlated to the behavioral disinhibition observed. In summary, these findings suggest that behavioral sensitization to nicotine
is associated with behavioral disinhibition and that chronic citalopram treatment counteracts the expression of both phenomena.
Since citalopram is a highly selective serotonin reuptake inhibitor, the effects of citalopram may be due to a facilitation
of serotonin neurotransmission caused by the chronic citalopram treatment.
Received: 2 December 1997/Final version: 16 August 1998 相似文献
4.
Rationale
Intermittent treatment of rats with psychomotor stimulants induces behavioral sensitization to their motor-stimulating effects. This sensitization involves an increase in mesolimbic and nigrostriatal dopamine release, and in male rats, facilitates sexual behavior.Objectives
The aim of this study is to investigate the effect of repeated injections of d-amphetamine on appetitive and consummatory sexual behaviors in female rats.Materials and methods
Sexually experienced or naïve females were injected with either d-amphetamine (1 mg/kg, i.p.) or saline every other day for three injections each. After each amphetamine injection, females were placed either in a bilevel testing chamber or in their home cages. After saline injections, females were placed in bilevel chambers. Following a 3-week washout period, females were tested for sexual behavior in bilevel chambers in a drug-free state.Results
Amphetamine pre-exposure facilitated the display of solicitations, hops and darts, and female–male mounting (FMM), regardless of whether the drug was paired with the testing environment.Conclusion
Intermittent amphetamine pretreatment that induces behavioral sensitization facilitates appetitive sexual behaviors in female rats, as has been shown previously in male rats. This suggests that the physiological substrates that modulate sensitized responses to psychomotor stimulants also mediate sensitized appetitive responses to sexual cues, including solicitation, hops and darts, and FMM. As in male rats, this facilitation was a direct consequence of amphetamine sensitization and not due to conditioned associations between drug and test environment.5.
Post-weaning housing conditions influence the behavioural effects of cocaine and d-amphetamine 总被引:4,自引:0,他引:4
Post-weaning social isolation can induce profound and long lasting effects on an animal’s behaviour. The present study investigated
the influence of post-weaning housing conditions on the sensitivity of rats to the behavioural effects of d-amphetamine and cocaine. The locomotor stimulant effects of both drugs were compared following acute and chronic administration.
The influence of post-weaning housing conditions on the effects of d-amphetamine and cocaine on responding for food and for a conditioned reinforcer were also examined. Isolated rats showed
enhanced locomotor activity on exposure to a novel environment. This difference was further exaggerated following administration
of d-amphetamine (0.5 mg/kg) and cocaine (5 mg/kg). Isolated, but not enriched, rats exhibited sensitisation to the locomotor
activating effects of repeated administration of a dose of 0.5 mg/kg d-amphetamine, whilst both groups sensitised equally to a dose of 1.0 mg/kg d-amphetamine. Rearing conditions did not affect sensitisation to cocaine (5, 10 mg/kg). Isolated rats exhibited a higher rate
of responding for a conditioned stimulus and for food on a progressive ratio schedule of reinforcement, both of which were
enhanced to a greater extent in isolates following administration of cocaine (5 mg/kg) and d-amphetamine (0.5 mg/kg). These results suggest that isolation rearing induces an enhancement in sensitivity to both the locomotor
stimulant and reinforcing properties of amphetamine and cocaine.
Received: 12 June 1996 / Final version: 17 October 1996 相似文献
6.
Lack of sensitization to the effects of d-amphetamine and apomorphine on sensorimotor gating in rats
This study assessed whether repeated injections of d-amphetamine or apomorphine could induce sensitization to the disruptive effects of these psychomotor stimulants on sensorimotor
gating in rats. In the first experiment, rats were given six pre-exposures to either 2.0 mg/kg d-amphetamine or saline before being tested for the effects of d-amphetamine (0.0, 0.5, 1.0, 2.0 or 4.0 mg/kg, IP) on prepulse inhibition of acoustic startle (PPI) and locomotor activity.
The tests for PPI confirmed that sensorimotor gating could be disrupted by a high dose of d-amphetamine (4.0 mg/kg). However, comparison of the dose-response curves for the drug and saline pre-exposed groups did not
reveal evidence for sensitization to this d-amphetamine effect in drug-pre-exposed rats, despite indications that sensitization had developed to the locomotor stimulant
effects of d-amphetamine. A similar pattern of results was obtained in a second experiment that examined the effects of apomorphine (0.0,
0.1, 0.2, 0.4 and 0.8 mg/kg, SC) on PPI and locomotion in rats pre-exposed to 2.0 mg/kg of this drug or its vehicle. These
findings demonstrate that treatments which induce sensitization to the behavioral activating effects of psychomotor stimulants
do not necessarily produce sensitization to the disruptive effects of stimulants on sensorimotor gating. The implications
of these results for hypotheses linking sensitization-like processes to the etiology of schizophrenia are discussed.
Received: 15 May 1997/Final version: 7 July 1997 相似文献
7.
We have shown that prior repeated exposure to d-amphetamine facilitates appetitive Pavlovian conditioning. However, animals sensitised in this manner also show elevated
levels of stimulated activity. To investigate whether enhanced conditioning was dependent upon increased activity, a conditioned
inhibition task was employed in the present study. Rats received d-amphetamine (2 mg/kg, IP) or vehicle once per day for 7 days. After a 7-day drug-free period, an activity assay confirmed
that repeated d-amphetamine treatment markedly elevated the locomotor response to a subsequent challenge with 0.5 mg/kg d-amphetamine. Conditioning began 6 days later. In phase 1, stimulus A+ (light or tone) immediately preceded sucrose availability
(excitatory conditioning). In phase 2, sucrose again was presented after A+ alone, but not after presentation of a compound
of A+ with a second stimulus (AB−). Sensitisation enhanced the acquisition of conditioned approach behaviour to the excitatory
stimulus A+ in phase 1. Furthermore, acquisition of conditioned inhibition to the stimulus compound, AB−, was also facilitated.
Thus, sensitised rats showed reduced levels of responding to the stimulus compound far sooner than controls. Finally, a retardation
test was carried out in stage 3, in which the inhibitory stimulus B- was paired alone with sucrose reward. Sensitised rats
initially showed retarded acquisition of excitatory conditioned responding relative to controls, suggesting that B possessed
stronger inhibitory associations in these animals. However, sensitised animals again exhibited higher levels of responding
in later sessions, consistent with the enhanced excitatory conditioning shown in phase 1. These findings suggest that prior
repeated d-amphetamine enhanced the acquisition of inhibitory and excitatory Pavlovian associations; a propensity not readily attributable
to stimulated locomotor hyperactivity.
Received: 29 December 1997/Final version: 21 July 1998 相似文献
8.
Rationale: Prepulse inhibition of the startle reflex (PPI) is attenuated in animals after administration of d-amphetamine and other drugs that stimulate mesolimbic dopamine activity. Objective: The aim of the present study was to evaluate the effects of d-amphetamine (20 mg) on a variety of psychophysiological and subjective measures, including PPI, in humans. Method: Thirty-six participants (18 women) participated in a double-blind, placebo controlled, repeated measures study. In one session,
participants received d-amphetamine (20 mg) orally, and in the other session, participants received an identical appearing placebo. Participants
were assessed at 60, 90, and 120 min after ingestion with a 5-min block of startle trials (six control trials and six prepulse
trials) followed by subjective measures of stimulation and mood. Results: d-Amphetamine increased subjective measures of stimulation and euphoria, attenuated PPI, and increased heart rate, relative
to placebo treatment. Conclusions: The effect of d-amphetamine on the subjective measures was substantial and consistent over time, while the effect on PPI was only observed
at 90 min after ingestion, and the effect on heart rate was limited to 90 and 120 min after ingestion.
Received: 22 June 1998/Final version: 23 November 1998 相似文献
9.
Previous studies have demonstrated that long-term administration of d-amphetamine produces a progressive augmentation of behavior. In the present experiment, rats receiving repeated systemic injections responded to an intraventricular infusion of d-amphetamine with an augmented increase in locomotor activity. These results indicate that central mechanisms, rather than peripheral dispositional factors, subserve the enhanced behavioral response to repeated amphetamine administration. 相似文献
10.
Matilde Valencia-Flores David N. Velázquez-Martínez Julían E. Villarreal 《Psychopharmacology》1990,102(1):136-144
The chronic exposure of rats to a schedule of operant water reinforcement coupled with chronically restricted access to water sensitized the animals to intermittentd-amphetamine injections (0.31–2.5 mg/kg with intervals of 12–23 days between any two injections) in such a way that this drug came to produce catastrophic losses of body weight (32.4% of control levels). In the sessions whend-amphetamine was administered, the rats were also given a total of 12 brief electric shocks. Loss of body weight was unaccompanied by parallel changes in operant behavior performance, or in food or water intake. Remarkably, in other studies with the same interventions (sham schedule sessions, water deprivation, and foot shocks), with the exception that reinforcers were never delivered,d-amphetamine did not produce catastrophic falls in body weight. This super-reactivity tod-amphetamine toxicity may be mediated by a possible stressor action of the schedule of reinforcement. Its mechanism might be analogous to the known sensitization produced by classical experimental stressor stimuli to the repeated administration ofd-amphetamine. 相似文献
11.
Rationale Psychostimulant drugs exert their behavioral effects primarily through enhancement of monoaminergic neurotransmission. Augmented
dopamine activity is thought to play a critical role in the psychomotor stimulant effects of amphetamine and cocaine, as well
as in the development of long-term behavioral sensitization evoked by repeated exposure to amphetamine. However, despite the
fact that brain dopamine and noradrenaline systems are closely interconnected, the extent to which noradrenergic transmission
contributes to these behavioral effects of psychostimulants is a relatively unexplored issue.
Objectives By inhibiting noradrenergic neurotransmission with the α2-adrenoceptor agonist clonidine, the α1-antagonist prazosin and the β-antagonist propranolol, we investigated the involvement of noradrenaline neurotransmission
in the psychomotor stimulant and long-term sensitizing effects of d-amphetamine and cocaine in rats.
Methods Clonidine (0.003–0.1 mg/kg), prazosin (0.1–3.0 mg/kg) and propranolol (1.0–3.0 mg/kg) were administered prior to d-amphetamine (1.0 mg/kg), cocaine (15 mg/kg) or apomorphine (1.0 mg/kg) and psychomotor activity was measured. In separate
studies, clonidine (0.03 mg/kg), prazosin (1.0 mg/kg) or propranolol (3.0 mg/kg) were co-administered with d-amphetamine (2.5 mg/kg) or cocaine (30 mg/kg) for 5 days, and locomotor sensitization was assessed 3 weeks post-treatment.
Results The psychomotor stimulant effect of d-amphetamine, but not that of cocaine or apomorphine, was dose-dependently inhibited by clonidine and prazosin, and enhanced
by propranolol. Clonidine, prazosin, and propranolol did not influence the induction of sensitization by amphetamine or cocaine.
Conclusions Enhancement of synaptic noradrenaline concentrations contributes to the psychomotor stimulant effect of d-amphetamine, but not cocaine or apomorphine. In addition, noradrenergic neurotransmission is not critically involved in the
induction of psychostimulant sensitization. 相似文献
12.
Activation of 5-HT1B receptors in the nucleus accumbens reduces amphetamine-induced enhancement of responding for conditioned reward 总被引:2,自引:2,他引:0
Previously, we have demonstrated that 5-hydroxytryptamine (5-HT) injected into the nucleus accumbens attenuates the potentiating
effects of d-amphetamine on responding for conditioned reward (CR). The present studies examined the 5-HT receptor involved in this effect
by investigating the effects of 5-HT agonists with differing affinities for 5-HT1 and 5-HT2 receptors on d-amphetamine-induced potentiation of responding for CR. Rats were trained to associate a light/tone stimulus (subsequently
the CR) with water delivery. In a test phase, they were allowed access to a lever delivering the CR, and an inactive (NCR)
lever. Responding on the CR lever was greater than responding on the NCR lever, indicating that the light/tone stimulus functioned
as a CR. Responding for the CR was selectively potentiated by injections of d-amphetamine (10 μg) into the nucleus accumbens. This effect was reduced by injections into the nucleus accumbens of 5-CT
(0.5 and 1 μg), RU24969 (10 μg), CP93,129 (1.25 and 2.5 μg) but not by DOI (10 μg) or 8-OH-DPAT (5 μg). The lower doses of
5-CT and CP93,129 did not reduce baseline responding for CR, or responding for water in a separate group of animals, indicating
that the effects of these drugs were behaviourally selective. The higher doses abolished the CR effect, and in the case of
5-CT and RU24969 also reduced responding for water. All of the effective drugs share in common the ability to stimulate 5-HT1B receptors, albeit with differing selectivities. The effect of CP93,129, the most selective of the 5-HT1B agonists, to inhibit the response-potentiating effect of d-amphetamine was reversed by the5-HT1B/1D antagonist GR127935 (3 mg/kg). The results indicate that activation of 5-HT1B receptors within the nucleus accumbens attenuates the effects of a dopamine-dependent behaviour, and that activation of these
receptors can oppose the behavioural effects of elevated mesolimbic dopamine transmission.
Received: 22 April 1998/Final version: 28 July 1998 相似文献
13.
Stimulating property of Turnera diffusa and Pfaffia paniculata extracts on the sexual behavior of male rats 总被引:1,自引:0,他引:1
Sexually potent and sexually sluggish/impotent male rats were treated orally with different amounts of Turnera diffusa and Pfaffia paniculata fluid extracts (0.25, 0.50, 1.0 ml/kg). While having no effect on the copulatory behavior of sexually potent rats, both plant
extracts – singly or in combination – improved the copulatory performance of sexually sluggish/impotent rats. The highest
dose of either extract (1 ml/kg) (as well as the combination of 0.5 ml/kg of each extract) increased the percentage of rats
achieving ejaculation and significantly reduced mount, intromission and ejaculation latencies, post-ejaculatory interval and
intercopulatory interval. Neither extract affected locomotor activity. These results seem to support the folk reputation of
Turnera diffusa and Pfaffia paniculata as sexual stimulants.
Received: 13 January 1998/Final version: 15 September 1998 相似文献
14.
Drugs of abuse produce amnestic effects in humans and laboratory animals in a variety of tasks. Generally, only a few compounds
have been examined in any particular procedure. It was the goal of the present studies to examine drugs of abuse of different
pharmacological classes in rats responding under two behavioral schedules historically employed as experimental models of
memory: spatial alternation and matching to position. One group of rats responded under a single-response spatial-alternation
baseline with a 10-s delay and another group responded under a matching-to-position baseline with delay values of 3, 10 and
30 s. Performance under the spatial-alternation baseline was characterized by low variability and >90% accuracy. Under the
matching-to-position baseline, saline control percent accuracy was >95% at 3 s, >85% at 10 s and >70% at 30 s. Under spatial
alternation cocaine, d-amphetamine, pentobarbital, diazepam, phencyclidine, scopolamine and methscopolamine produced significant (P<0.05) effects on accuracy, whereas only cocaine, d-amphetamine, pentobarbital and phencyclidine disrupted accuracy under the matching-to-position baseline. These results suggest
that spatial alternation may be a more sensitive baseline for determining drug effects on working memory in the rat.
Received: 16 April 1997 / Final version: 25 November 1997 相似文献
15.
The present experiment evaluated the ability of the 5-HT3 antagonist, ondansetron, administered during chronic cocaine administration, to block the development of sensitization and
tolerance induced by the intermittent or continuous administration of cocaine, respectively. Rats were pretreated with 40 mg/kg
per day cocaine for 14 days by either SC injections or osmotic minipumps, or 0.9% saline, administered by SC injection. During
this chronic (cocaine) treatment, all rats received a daily SC injection of 0–1.0 mg/kg ondansetron. The rats were then withdrawn
from the pretreatment regimen for 7 days. On day 7 of withdrawal from the cocaine pretreatment all subjects received a 15.0 mg/kg
IP cocaine challenge, and their behavior was then rated according to the modified Ellinwood and Balster scale for 60 min.
The results indicated that daily injections of ondansetron had no consistent or significant effect on the subsequent behavioral
response to cocaine in the saline control subjects. In contrast, daily injections of ondansetron with cocaine significantly
blocked the development of sensitization with an inverted U-shape dose-response curve. In the continuous cocaine group ondansetron
injections also attenuated the development of behavioral tolerance. The results therefore indicate that 5-HT3 receptor stimulation during continuous and intermittent cocaine administration is an important link in the development of
behavioral tolerance and sensitization.
Received: 1 July 1996/Final version: 25 September 1996 相似文献
16.
The present study examined the ability of pretreatment with MK-801 or haloperidol to block the induction of behavioral sensitization to amphetamine challenge by repeated immobilization stress in male Sprague-Dawley rats. Fifteen minutes before each of ten 30-min restraint sessions, rats were administered saline, MK-801 (0.01, 0.10 or 0.25 mg/kg IP) or haloperidol (0.10 or 0.25 mg/kg IP). Control rats received the same injection regimen without restraint. An additional experiment examined the ability of MK-801 to block the induction of sensitization by repeatedd-amphetamine. In this experiment, rats were administered saline or MK-801 (0.25 mg/kg IP) 15 min before each of ten amphetamine injections (1.0 mg/kg IP, administered under the same regimen as immobilization stress). Four days after the final immobilization or amphetamine injection, rats were tested for locomotor response to novelty, saline andd-amphetamine (1.5 mg/kg IP). Exposure to repeated immobilization stress significantly enhanced the locomotor response to amphetamine challenge but not to saline challenge whether rats were pretreated with saline, MK-801 or haloperidol. Secondary analysis of dose effects in each pretreatment group revealed that at 0.25 mg/kg, repeated MK-801 in itself induced sensitization to the response to amphetamine in control rats and potentiated stress-induced sensitization in restrained rats. In contrast, the sensitization induced by repeated amphetamine was attenuated by MK-801 pretreatment. Neither dose of haloperidol affected the locomotor response to saline or amphetamine in control or stressed rats. These results indicate that the effects of MK-801 on the induction of sensitization are complex and suggest that amphetamine-and stress-induced behavioral sensitization may arise through different mechanisms. 相似文献
17.
The present experiment evaluated the ability of the 5-HT3 antagonist, ondansetron, administered during withdrawal from chronic cocaine administration, to block the expression of sensitization
and tolerance induced by the intermittent or continuous administration of cocaine, respectively. Rats were pretreated with
40 mg/kg/per day cocaine for 14 days by either SC injections or osmotic minipumps, or 0.9% saline, administered via osmotic
minipump. During the first 5 days of withdrawal from this pretreatment regimen, all rats received a daily SC injection of
0–1.0 mg/kg ondansetron. On day seven of with-drawal from the cocaine pretreatment (2 days after the final ondansetron injection)
all subjects received a 15.0 mg/kg IP cocaine challenge. Their behavior was then rated according to the Ellinwood and Balster
(1974) scale for 60 min. The results indicated that daily injections of ondansetron, on days 1–5 of withdrawal from the pretreatment
regimen, had no significant effect on the subsequent behavioral response to cocaine in the saline control subjects. In contrast,
daily injections of ondansetron, on days 1–5 of withdrawal from intermittent cocaine administration, significantly blocked
the expression of sensitization. In the continuous cocaine group, ondansetron injections, on days 1–5 of withdrawal from continuous
cocaine administration, also blocked the expression of behavioral tolerance. The results therefore indicate that changes in
5-HT3 receptor function are associated with the expression of tolerance and sensitization, respectively.
Received: 1 April 1997/Final version: 28 July 1997 相似文献
18.
Félix Carvalho Eduarda Fernandes Fernando Remião Maria Lourdes Bastos 《Archives of toxicology》1999,73(2):83-89
The purpose of this study was to evaluate rat tissue antioxidant status after repeated administration of d-amphetamine. Three groups of four rats each were used: control, d-amphetamine sulphate dosed (s.c., 20 mg/kg per day), and pair-fed. After 14 days of d-amphetamine daily administration, superoxide dismutase (CuZnSOD and MnSOD), catalase, glutathione peroxidase (GPx), glutathione
reductase (GRed), glutathione-S-transferase (GST), glutathione (GSH), cysteine and thiobarbituric acid reactive substances
(TBARS) were measured in liver, kidney, and heart. Various serum and urine parameters were also analysed. d-Amphetamine treatment induced an increase of liver GSH, as well as a decrease of cysteine and MnSOD levels in this organ.
A small increase in serum transaminases was also observed in comparison to the pair-fed group. Hepatic levels of TBARS, GPx,
GRed and CuZnSOD were found to be similar among the three groups of rats. d-Amphetamine treatment induced an increase of kidney GST, GRed and catalase levels, and an elevation of N-acetyl-β-d-glucosaminidase efflux to the urine, accompanied by a decrease in urinary creatinine, compared to the pair-fed group. In
d-amphetamine treated animals, heart cysteine levels were significantly depleted when compared to the pair-fed group, but all
three groups of rats were found to have similar heart antioxidant enzyme levels. These results indicate that repeated administration
of d-amphetamine caused a certain degree of stress in liver and kidney, which was followed by adaptations of antioxidant defences.
The mechanisms involved in d-amphetamine-induced toxicity may explain the different adaptations observed for the studied organs.
Received: 19 October 1998 / Accepted: 11 January 1999 相似文献
19.
R. Spanagel Inge Sillaber Walter Zieglgänsberger William A. Corrigall Jane Stewart Yavin Shaham 《Psychopharmacology》1998,139(4):391-401
Acamprosate (calcium-acetyl homotaurinate) is a new compound used in the treatment of alcohol abuse. Because of the putative
link between alcoholism and the endogenous opioid systems in both humans and laboratory animals, we tested in rats the effects
of acamprosate on behavioral and neurochemical effects of opioid drugs related to their abuse potential. These included sensitization
to the behavioral effects of morphine, morphine-induced dopamine (DA) release in the nucleus accumbens (NAS), intravenous
(IV) heroin self-administration and relapse to heroin seeking in drug-free rats. In experiment 1, rats were injected daily
with either morphine (10 mg/kg, SC) or saline for 14 days. Three days later in a test for the expression of sensitization,
an injection of morphine (10 mg/kg) resulted in increased locomotor activity and enhanced DA release in the NAS in rats previously
exposed to morphine. Acamprosate (two injections of 200 mg/kg; 12 h apart; IP) suppressed the expression of the sensitized
responses, but did not alter the effects of morphine in drug-naive control rats. In experiment 2, it was found that acamprosate
(two injections of 50–200 mg/ kg; IP) had no consistent effects on IV heroin self-administration (50–100 μg/kg per infusion)
and, in experiment 3, that acamprosate (100–200 mg/ kg, IP) did not alter reinstatement of drug seeking induced by priming
injections of heroin (0.25 mg/kg, SC) or a footshock stressor (15 min; 0.5 mA) after a 5- to 8-day period of extinction. Thus,
although acamprosate attenuated the expression of sensitized locomotor activity and DA release in the NAS, it did not have
any consistent effect on either the intake of heroin during the maintenance phase or the relapse to heroin seeking in a drug-free
state. Thus, to the extent that the self-administration and the reinstatement procedures provide valid preclinical models
for drug use and relapse in humans, our data suggest that acamprosate may not be effective in altering drug-taking behavior
in heroin users.
Received: 4 November 1997/Final version: 25 January 1998 相似文献
20.
In this study, effects of histamine (HA) agents on methamphetamine (METH)-induced stereotyped behavior and behavioral sensitization
were examined in rats. Pretreatment with a precursor of HA, L-histidine (750 mg/kg), significantly inhibited the METH (3 mg/kg)-induced stereotyped behavior, whereas pretreatment with
an inhibitor of HA synthesis, α-fluoromethylhistidine (FMH) (100 mg/kg), an H1 antagonist pyrilamine (5 mg/kg) or an H2 antagonist zolantidine (5 mg/kg) enhanced it. The inhibitory effect of L-histidine on METH-induced stereotyped behavior was significantly blocked by coadministration of pyrilamine and zolantidine,
indicating that the effect is mediated through H1 and H2 receptors. Moreover, chronic treatment with METH (3 mg/kg) significantly enhanced stereotyped behavior at the rechallenge
with METH (1 mg/kg). Chronic treatment with L-histidine (750 mg/kg) plus METH inhibited the METH-induced argumentation of stereotyped behavior, while that with FMH (100 mg/kg),
pyrilamine (5 mg/kg) or zolantidine (5 mg/kg) potentiated it. These findings suggest that the HA neuron system has an inhibitory
role in METH-induced stereotyped behavior and behavioral sensitization.
Received: 1 July 1996/Final version: 26 November 1996 相似文献