噻诺啡灌胃对小鼠吗啡行为敏化的影响

目的研究ig噻诺啡对小鼠吗啡行为敏化的影响。方法测定小鼠的自主活动，观察ig噻诺啡对小鼠自主活动及急性给予吗啡所诱导小鼠活动增强效应的影响；建立小鼠吗啡行为敏化模型，观察ig噻诺啡对行为敏化形成、转化及表达的影响。结果单次ig噻诺啡(1.25-5.0 mg·kg^-1)可剂量依赖性地降低小鼠的自主活动(P<0.01)，但多次给药可产生耐受。噻诺啡可有效地抑制急性给予吗啡所诱导的小鼠高活动性(P<0.05)及小鼠吗啡行为敏化的形成、转化和表达(P<0.05或P<0.01)。结论噻诺啡可抑制小鼠中枢神经系统，对阿片类药物的滥用和成瘾可能具有干预作用。     

地高辛对小鼠吗啡行为敏化的影响

目的:探讨地高辛对小鼠吗啡行为敏化的影响.方法:测定小鼠的自主活动,观察地高辛对小鼠自主活动的影响.急性吗啡(10 mg·kg-1,ip)处理小鼠前给予地高辛,观察地高辛对急性吗啡引起小鼠高活动性的影响.慢性吗啡处理小鼠,建立吗啡行为敏化模型,观察地高辛对吗啡行为敏化的影响.结果:(1)地高辛(0.5 mg·kg-1-...     

噻诺啡灌胃给药对小鼠甲基苯丙胺行为敏化的影响

目的:探讨新型丁丙诺啡同系物-噻诺啡,灌胃(ig)给药对小鼠甲基苯丙胺行为敏化过程的影响。方法:测定小鼠的自主活动,观察ig噻诺啡对小鼠的自主活动及单次给予甲基苯丙胺所诱导的小鼠高活动性的影响。建立甲基苯丙胺诱导的小鼠行为敏化模型,观察噻诺啡对行为敏化形成、转化及表达的影响。结果:(1)单次ig噻诺啡(1 2 5 - 5 0mg·kg-1)可剂量依赖性地抑制小鼠的自主活动(P <0 . 0 1) ,其作用多次给药后产生耐受;(2 )噻诺啡对单次给予甲基苯丙胺所诱导的小鼠的高活动性无明显影响;(3)噻诺啡对甲基苯丙胺诱导小鼠行为敏化的形成和表达无明显作用,却可显著抑制敏化的转化过程(P <0 . 0 5 )。结论:ig噻诺啡可抑制小鼠中枢神经系统,阻断甲基苯丙胺诱导小鼠产生行为敏化的转化过程,提示噻诺啡对甲基苯丙胺的成瘾行为具有一定的干预作用。     

Y-IP5对小鼠吗啡行为敏化和条件性位置偏爱的影响

目的探讨新型化合物Y-IP5对吗啡诱导小鼠行为敏化和条件性位置偏爱(conditioned place preference,CPP)的影响。方法测定小鼠的自发活动,观察Y-IP5对小鼠自发活动及急性给予吗啡所诱导小鼠高活动性的影响;慢性吗啡处理小鼠,建立小鼠吗啡行为敏化和CPP模型,观察Y-IP5对行为敏化形成、转化、表达及CPP形成的影响。结果单次或多次给予Y-IP5都不影响小鼠的自发活动,但能抑制急性给予吗啡所致的小鼠高活动性(P<0.05);Y-IP5本身不诱导小鼠形成行为敏化和CPP,但能抑制吗啡诱导小鼠形成行为敏化和CPP(P<0.05),但Y-IP5对吗啡诱导小鼠行为敏化的转化和表达无抑制作用。结论Y-IP5对阿片类药物的精神依赖可能具有干预作用。     

归元片对小鼠吗啡行为敏化的影响

目的 :探讨中药复方制剂归元片对吗啡行为敏化的影响。方法 :测定小鼠的自主活动 ,观察归元片对小鼠自主活动的影响。给小鼠慢性吗啡处理 ,建立吗啡诱导的行为敏化小鼠模型 ,观察归元片对吗啡行为敏化的影响。结果 :(1)归元片 (2 5 - 10g·kg- 1 )明显抑制小鼠的自主活动 ,并呈剂量依赖性 ;(2 )归元片剂量依赖性地阻断小鼠吗啡行为敏化的获得和表达 ,但对行为敏化的转换无影响。结论 :归元片对中枢神经系统具有抑制作用 ,可以阻止吗啡成瘾行为的形成 ,对吗啡诱导的敏化行为具有抑制作用。提示归元片对吗啡的精神依赖性可能具有干预作用     

Morphine-induced sensitization in mice: changes in locomotor activity by prior scheduled exposure to GABAA receptor agents

This study investigated the effects of a gamma-amino-butyric acid type A (GABAA) receptor agonist and antagonist on morphine-induced locomotor sensitization in male albino mice. Subcutaneous administration to mice of a high dose of morphine (30 mg/kg), but not lower doses (5, 10 and 20 mg/kg) increased locomotion. The maximum locomotor activity was achieved during a 20-min measurement period. The locomotor response to a low dose of morphine (5 mg/kg, subcutaneously) given on day 9 was enhanced in mice pretreated with morphine (7.5, 15 and 30 mg/kg/day x 3 days), indicating that sensitization had developed. Three-day intracerebroventricular (i.c.v.) administration of the GABAA receptor agonist, muscimol (0.025, 0.05, 0.1 and 0.2 microg/mouse/day) significantly decreased both morphine-induced motor stimulation and locomotor sensitization. On the other hand, a 3-day pretreatment with the GABAA-receptor antagonist, bicuculline (0.25, 0.5 and 1 microg/mouse/day) reduced morphine (15 mg/kg)-induced locomotor sensitization. Repeated i.c.v. injections of a lower dose of bicuculline (0.25 microg/mouse/day x 3 days) by itself also decreased morphine-induced locomotion. Furthermore, repeated i.c.v. administration of bicuculline (0.25, 0.5 and 1 microg/mouse/day x 3 days) decreased the effect of i.c.v. injection of muscimol (0.1 microg/mouse/day x 3 days) on locomotor activity induced by morphine (5 mg/kg) in both control and sensitized mice. The magnitude of this response was, however, variable. The results indicate that GABAA receptors might be involved in the acquisition of morphine-induced sensitization.     

眼镜蛇毒粗毒毒素Ⅳ对小鼠吗啡行为敏化的影响

目的 探讨眼镜蛇毒毒素Ⅳ对吗啡行为敏化的影响.方法 测定小鼠自主活动,观察毒素Ⅳ对小鼠自主活动影响.昆明种小鼠慢性吗啡处理,建立吗啡诱导行为敏化模型,观察毒素Ⅳ对吗啡行为敏化影响.结果 毒素Ⅳ(0.027、0.04、0.08 mg/kg)腹腔注射后,均能减少小鼠自主活动,降低吗啡诱导的高活动性,抑制小鼠吗啡行为敏化的获得,阻断小鼠吗啡行为敏化表达,其中中、高剂量毒素Ⅳ作用较显著.结论 毒素Ⅳ对中枢神经系统具有抑制作用,可以阻止吗啡成瘾行为形成,对吗啡诱导的敏化行为具有抑制作用,提示毒素Ⅳ对吗啡精神依赖性可能具有干预作用.     

Role of nitric oxide in the acquisition and expression of apomorphine- or morphine-induced locomotor sensitization

In the present study, the effects of L-arginine, a nitric oxide (NO) precursor, and N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, on apomorphine- or morphine-induced locomotor sensitization in male albino mice were investigated. Our data showed that subcutaneous (s.c.) injection of apomorphine (2-10 mg/kg) or morphine sulphate (5-50 mg/kg) significantly increased locomotor behaviour in a dose-dependent manner. Intraperitoneal (i.p.) administration of L-arginine (100 mg/kg) increased locomotor activity, whereas L-NAME (20 mg/kg) decreased it. L-Arginine and L-NAME increased and decreased apomorphine- or morphine-induced locomotions, respectively. The locomotor behavioural response was enhanced in mice pretreated with apomorphine (2 mg/kg, daily x3 days) or morphine (10 mg/kg, daily x3 days) alone, indicating that sensitization had developed. Administration of L-arginine 30 min before each of three daily doses of apomorphine or morphine increased the development of sensitization, while administration of L-NAME 30 min before each of three daily doses of apomorphine or morphine decreased the acquisition of sensitization induced by apomorphine or morphine. Administration of L-arginine significantly increased and L-NAME significantly and dose-dependently decreased the expression of both apomorphine- and morphine-induced sensitization. The results indicate that NO may be involved in the acquisition and expression of apomorphine- or morphine-induced sensitization.     

5-羟色胺酸对吗啡诱导小鼠行为敏化的影响

研究中枢5-羟色胺能系统对吗啡诱导小鼠行为敏化的介导作用。选用雄性昆明小鼠，每天2次注射生理盐水或吗啡10mg／kg，连续3天。停药5天后，于第9天，进行吗啡激发试验，测定小鼠的自主活动60min，观察行为敏化效应。此外，选用5-羟色胺前体物质5-羟色氨酸作为工具药，分别在吗啡处理阶段（形成期），吗啡停药阶段（转换期）以及吗啡激发试验前腹腔注射20-80mg／kg5-羟色氨酸。激发试验给予吗啡后，立即测定小鼠的自主活动。实验第9天激发试验数据表明，每天2次反复给予吗啡的小鼠，其自主活动明显高于生理盐水对照组，说明小鼠对吗啡产生了行为敏化效应。5-羟色氨酸可以选择性抑制吗啡对小鼠行为敏化的诱导作用，其抑制作用呈剂量依赖性。然而，5-羟色氨酸对小鼠吗啡行为敏化的转换和表达无明显药理作用。因此，中枢5-羟色胺能系统的功能水平上调可能对吗啡诱导小鼠行为敏化效应具有一定的抑制作用。     

槟榔碱对小鼠吗啡行为敏化的影响

目的:探讨槟榔嚼块的主要成分—槟榔碱,对小鼠吗啡行为敏化过程的影响。方法:测定小鼠的自主活动,观察ip槟榔碱对小鼠的自主活动及单次给予吗啡所诱导的小鼠高活动性的影响;建立吗啡诱导的小鼠行为敏化模型,观察槟榔碱对行为敏化形成、表达的影响。结果:(1)单次ip槟榔碱(0·25-2·0mg·kg-1)可剂量依赖性地抑制小鼠的自主活动(P<0·05),多次给药后这种抑制作用既不产生耐受,也不形成敏化;(2)槟榔碱(2·0mg·kg-1)可增强单次给予吗啡所诱导的小鼠的高活动性(P<0·05);(3)槟榔碱(2·0mg·kg-1)可增强吗啡诱导小鼠行为敏化的形成(P<0·05);(4)虽然槟榔碱(2·0mg·kg-1)多次给药降低吗啡诱导小鼠行为敏化表达的程度(P<0·05),但是槟榔碱(0·5-2·0mg·kg-1)单次给药不影响吗啡诱导小鼠行为敏化的表达。结论:槟榔嚼块中的主要成分槟榔碱能增强小鼠吗啡诱导的急性高活动性和吗啡行为敏化的形成,提示槟榔嚼块有可能增强吗啡的成瘾性。     

Influence of morphine and dopamine receptor sensitization on locomotor activity in mice

In the present study, the influence of morphine- and dopamine receptor antagonists-induced sensitization on morphine-induced locomotion in mice was investigated. Morphine (30, 40 and 50 mg/kg) increased, while lower doses of the opioid (10 and 20 mg/kg) decreased locomotor activity of mice. Subchronic repeated pretreatment of animals with morphine showed an increase in locomotion induced by the opioid. Clozapine reduced locomotor activity induced by morphine in both the na?ve and subchronic morphine-treated animals. Subchronic pretreatment of clozapine also caused an increase in the locomotion induced by morphine. Sulpiride also decreased locomotion induced by morphine and its subchronic administration of the drug caused an increase in morphine- or apomorphine-induced locomotion. Co-administration of clozapine with sulpiride did not elicit potentiation in inhibiting the morphine effect. The D2 receptor mRNA expression was also increased by repeated morphine administration. It may be concluded that morphine-induced sensitization may be due to increase in D2 receptor mRNA expression. Sulpiride and clozapine may induce sensitization and also inhibit morphine-induced locomotion through their dopamine receptor blocking properties.     

Attenuating effect of adenosine receptor agonists on the development of behavioral sensitization induced by sporadic treatment with morphine

The aim of the study is to investigate the effect of adenosine receptor agonists on the development of morphine-induced sensitization to the locomotor activity of mice. Selective A1 (N⁶-cyclopentyladenosine - CPA) and A2A (2-p-(2-carboxyethyl) phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride - CGS 21680) adenosine receptor agonists or non-selective A1/A2A (5'-N-ethylcarboxamidoadenosine - NECA) adenosine agonists as representatives of adenosinergic drugs have been used in the experiment. Behavioral sensitization has been obtained by sporadic treatment with morphine (10.0 mg/kg, i.p.). We have shown that adenosine receptor agonists co-administered with morphine significantly attenuates increase in the locomotor activity of mice evoked by challenge dose of morphine. These effects have been observed after stimulation of the selective A1 or A2A and non-selective A1/A2A adenosine receptors, namely both receptors were involved in morphine-induced sensitization. Thus, we have demonstrated that adenosine agonists are able to inhibit behavioral sensitization induced by sporadic applications of morphine.     

诺米芬新对慢性吗啡处理后小鸡自发活动量的影响

目的 :探求吗啡对刚出生的小鸡自发活动量的影响以及行为敏感化的多巴胺神经机制。方法 :连续 7d每天给予小鸡ip不同剂量的吗啡 (5、10、2 0mg·kg- 1 ) ,观察其行为敏感化效应 ,撤药 3d后观察多巴胺转运体阻断剂诺米芬新 (0 5、1mg·kg- 1 )的干预效果。结果 :反复给药后 ,5mg·kg- 1 吗啡显著增加小鸡的自发活动量 (P <0 0 5 ,P <0 0 1) ,而且其自发活动量随给药次数的增多而不断增高 ;2 0mg·kg- 1 吗啡则明显降低小鸡的自发活动量 (P <0 0 5 )。诺米芬新呈剂量依赖性增加 5mg·kg- 1 组小鸡的自发性活动量 (P <0 0 5 )。结论 :反复小剂量吗啡处理能够导致鸟类行为敏感化效应 ,多巴胺可能在其中起重要作用。     

Inhibition of muscimol on morphine-induced hyperactivity,reverse tolerance and postsynaptic dopamine receptor supersensitivity

This study was performed to investigate the effect of muscimol on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity in mice. A single administration of morphine induced hyperactivity as measured in mice, and the morphine-induced hyperactivity was inhibited dose-dependently by the administration of the GABA(A) agonist, muscimol (0.3, 0.5 and 1.0 mg kg(-1) i.p.). However, daily repeated administration of morphine caused the development of reverse tolerance against morphine hyperactivity (10 mg kg(-1) s.c.). The administration of muscimol inhibited the development of reverse tolerance against morphine hyperactivity (10 mg kg(-1) s.c.) in mice that had received chronic administration of morphine. Postsynaptic dopamine receptor supersensitivity, as shown by the enhanced ambulatory activity after administration of apomorphine (2 mg kg(-1) s.c.), also developed in reverse-tolerant mice. Muscimol also inhibited the development of postsynaptic dopamine receptor supersensitivity induced by the chronic administration of morphine. These results suggest that the hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity induced by morphine can be inhibited via the activation of GABA(A) receptors.     

The effect of acamprosate on the development of morphine-induced behavioral sensitization in rats

Recently we have shown that the alcohol anti-craving drug acamprosate (calcium acetylhomotaurinate), a functional N-methyl-D-aspartate (NMDA) receptor antagonist which is used therapeutically to prevent relapse in weaned alcoholics, was also effective in suppressing (1) conditioned place aversion induced by morphine withdrawal, and (2) expression of morphine-induced behavioral sensitization. Here, we addressed the question of whether the development of behavioral sensitization, induced by daily injections of morphine (10 mg/kg) over a period of 10 days, could also be suppressed by repeated pretreatment with acamprosate (200 mg/kg). Repeated intermittent injections of morphine produced sensitization of locomotor activity and sniffing behavior. Acamprosate did not block the development of morphine-induced behavioral sensitization. This lack of effect on the development of this phenomenon is inconsistent with the view that NMDA receptor antagonists block the development of sensitization. We suggest that this may derive from the relatively low NMDA receptor-specific antagonism of acamprosate as compared to other NMDA receptor antagonists used in this model. In conclusion, the effect of acamprosate on morphine-induced behavioral sensitization seems to be restricted to the expression of this phenomenon.     

Repeated alcohol: behavioral sensitization and alcohol-heightened aggression in mice

RATIONALE: Repeated administration of psychomotor stimulants or opiates can induce behavioral sensitization, typically detected as progressive and long-lasting increases in the motor-activating effects of these drugs. This phenomenon may be relevant to seizure susceptibility, drug self-administration, and sexual behavior. Repeated administration of alcohol can also induce behavioral sensitization and may have consequences on how alcohol affects aggressive behavior. OBJECTIVES: To (1) determine the enduring nature of locomotor sensitization to alcohol; (2) examine subsequent changes to morphine and amphetamine effects on locomotor behavior; and (3) test whether behavioral sensitization to alcohol or morphine is relevant to alcohol-heightened aggression. METHODS AND RESULTS: In the first experiment, male CFW mice were given ten injections of alcohol (2.4 g/kg/day), morphine (30.0 mg/kg/day), or saline. Video tracking confirmed locomotor sensitization--an approximate 200% increase in the motor-stimulating effects of these drugs. Challenges with 2.0 g/kg alcohol revealed that locomotor sensitization to alcohol persisted for at least 2 months. Alcohol-sensitized mice showed evidence of cross-tolerance to the sedative effects of morphine (5 mg/kg) but showed no evidence of cross-sensitization to the stimulant effects of 30.0 mg/kg morphine or 1.0 mg/kg amphetamine. In the second experiment, under conditions resulting in species-typical aggressive behavior against a male intruder, there were no differences in the aggressive behavior relative to saline control mice following alcohol or morphine sensitization. However, in the mice sensitized to alcohol, but not to morphine, there was a vertical shift in the dose-effect curve for moderate doses of alcohol (0.6-1.7 g/kg, p.o.). In addition, twice as many alcohol-sensitized mice consistently showed alcohol-heightened aggression when compared with the saline control mice (74% vs 37%, respectively). CONCLUSIONS: Repeated administration of alcohol can sensitize locomotor stimulation and may also render mice more vulnerable to increased aggression after alcohol. Moreover, the results suggest that at least some of the neuroadaptations caused by repeated administration of alcohol are relevant to alcohol-heightened aggression.     

Blockade of morphine-induced behavioral sensitization by a combination of amisulpride and RB101, comparison with classical opioid maintenance treatments

BACKGROUND AND PURPOSE: Maintenance treatments with methadone or buprenorphine are more or less efficient procedures for helping heroin addicts to stop or reduce drug abuse. Another approach to treat opiate dependence could be to target the endogenous opioid system by enhancing the effects of enkephalins by protecting them from enzymic degradation by the dual peptidase inhibitor RB101. EXPERIMENTAL APPROACH: As chronic treatment with the dopamine D2 antagonist amisulpride facilitates RB101-induced behavioral effects, we chose in this study to treat mice previously sensitized to the hyperlocomotor effects induced by morphine with a combination of amisulpride and RB101. KEY RESULTS: Expression of morphine-induced locomotor sensitization was abolished after combined treatment with amisulpride (20 mg x kg(-1), i.p.) and RB101 (80 mg x kg(-1), i.p.), whereas these drugs were not effective when used alone. We then compared these results with the effects of amisulpride combined with buprenorphine (0.1 mg x kg(-1), i.p.) or methadone (2.5 mg x kg(-1), i.p.) upon morphine-induced behavioral sensitization. Whereas the combination of amisulpride and buprenorphine partially blocked the expression of morphine sensitization, amisulpride+methadone was not effective in this paradigm. CONCLUSIONS AND IMPLICATIONS: The combination of amisulpride+RB101 appears to be very efficient in blocking the expression of morphine-induced behavioral sensitization. This could reflect a reinstatement of a balance between the function of the dopamine and opioid systems and could represent a new approach in maintenance treatments for opiate addiction.     

Inhibitory effects of glycine on morphine-induced hyperactivity,reverse tolerance and postsynaptic dopamine receptor supersensitivity in mice

The effects of glycine on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity in mice was examined. A single administration of morphine (10 mg/kg, s.c.) induced hyperactivity as measured in mice. The morphine-induced hyperactivity was inhibited by pretreatment with glycine (100, 200 and 400 mg/kg, i.p.). In addition, it was found repeated administration of morphine (10 mg/kg, s.c.) to mice daily for 6 days caused an increase in motor activity which could be induced by a subsequent morphine dose, an effect known as reverse tolerance or sensitization. Glycine (100, 200 and 400 mg/kg, i.p.) also inhibited morphine-induced reverse tolerance. Mice that had received 7 daily repeated administrations of morphine also developed postsynaptic dopamine receptor supersensitivity, as shown by enhanced ambulatory activity after administration of apomorphine (2 mg/kg, s.c.). Glycine inhibited the development of postsynaptic dopamine receptor supersensitivity induced by repeated administration of morphine. It is suggested that the inhibitory effects of glycine might be mediated by dopaminergic (DAergic) transmission. Accordingly, the inhibition by glycine of the morphine-induced hyperactivity, reverse tolerance and dopamine receptor supersensitivity suggests that glycine might be useful for the treatment of morphine addiction.     

The involvement of noradrenergic transmission in the morphine-induced locomotor hyperactivity in mice withdrawn from repeated morphine treatment.

1. Our previous studies suggest that in addition to the cerebral dopaminergic systems the noradrenergic ones have a crucial role in the morphine-induced behavioural sensitization in mice. Therefore the effects of alpha2-adrenoceptor antagonist, idazoxan (1 and 3 mg kg(-1), i.p.) on morphine-induced locomotor hyperactivity as well as on morphine-induced changes in cerebral noradrenaline (NA) and striatal dopamine (DA) metabolism were studied in mice withdrawn for 3 days from 5 day repeated morphine treatment. The concentrations of NA, free 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG), DA, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 3-methoxytyramine (3-MT) were determined. 2. Acute morphine (10 mg kg(-1), s.c.) increased locomotor activity in control and in morphine-withdrawn mice; idazoxan alone did not alter the activity. Idazoxan pretreatment did not alter the locomotor hyperactivity induced by acute morphine in control mice but potentiated it in morphine-withdrawn mice. 3. Acute morphine elevated MOPEG less but increased DOPAC and HVA more clearly in morphine-withdrawn mice than in controls, and decreased 3-MT only in controls. Idazoxan alone did not alter the NA or DA metabolite concentrations in control mice, but elevated MOPEG as well as DOPAC in morphine-withdrawn mice. 4. In control mice idazoxan enhanced acute morphine's elevating effect on MOPEG. In withdrawn mice idazoxan counteracted the tolerance so that acute morphine elevated MOPEG in these mice to about similar level as in controls. 5. Idazoxan pretreatment abolished the HVA increasing effect of acute morphine both in control and withdrawn mice. In control mice idazoxan enhanced morphine's elevating effect on DOPAC and abolished morphine's decreasing effect on 3-MT. Idazoxan did not alter morphine's effects on DOPAC or 3-MT concentrations in withdrawn mice. 6. Our results show that in morphine-withdrawn mice idazoxan pretreatment reveals the morphine-induced locomotor sensitization. This most probably occurs by overcoming the tolerance towards the acute morphine-induced increase of cerebral NA turnover and release. It is suggested that in mice the cerebral noradrenergic in addition to the dopaminergic systems are major determinants of the behavioural sensitization to morphine.     

Prior morphine exposure enhances ibogaine antagonism of morphine-induced locomotor stimulation

Ibogaine is currently being investigated for its potential use as an anti-addictive agent. In the present study we sought to determine whether prior morphine exposure influences the ability of ibogaine to inhibit morphine-induced locomotor stimulation. Female Sprague-Dawley rats were pretreated once a day for 1–4 days with morphine (5, 10, 20 or 30 mg/kg, IP) or saline and then received ibogaine (40 mg/kg, IP) 5 h after the last morphine pretreatment dose. Compared to rats pretreated with saline, rats pretreated with morphine (10, 20 or 30 mg/kg, IP) before ibogaine (40 mg/kg, IP) showed a significant reduction in morphine-induced (5 mg/kg, IP) locomotor stimulation when tested 19 h after ibogaine administration. Furthermore, this effect was apparent over a range of ibogaine (5–60 mg/kg, IP) and morphine test (2.5–5 mg/kg, IP) dosages. Doses of ibogaine (5 and 10 mg/kg, IP) which alone were inactive inhibited morphine-induced locomotor activity when rats had been pretreated with morphine. These results, showing that morphine pre-exposure affects ibogaine activity, suggest that variable histories of opioid exposure might account for individual differences in the efficacy of ibogaine to inhibit opioid addiction.