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T J De Vries

Publications and source records attributed to T J De Vries.

At least 19 recordsLinked to original sources
PubMed2006

Interactions between CB1 cannabinoid and mu opioid receptors mediating inhibition of neurotransmitter release in rat nucleus accumbens core.

We examined the occurrence of functional interactions between CB1 cannabinoid and mu opioid receptors in the core of rat nucleus accumbens (NAc core). To that end, receptor-mediated inhibition of depolarization (4-aminopyridine)-induced [3H]glutamate release and glutamate (NMDA) receptor-stimulated [14C]acetylcholine (ACh) and [3H]GABA release was studied in superfused NAc core slices. The inhibitory effects of the mu receptor agonist morphine and the CB1 receptor agonist HU210 on the release of these neurotransmitters were selectively antagonized by the mu receptor antagonist naloxone and the CB1 receptor antagonist SR141716A, respectively. Surprisingly, naloxone prevented the antagonistic action of SR141716A at CB1 receptors and SR141716A abolished that of naloxone at mu receptors mediating inhibition of [3H]glutamate and [3H]GABA release. Therefore, these antagonists seem to allosterically interact, indicating the involvement of physically associated mu opioid and CB1 cannabinoid receptors. Such an interaction between antagonists was not observed at the receptors mediating inhibition of [14C]ACh release. Moreover, dose-response curves of the agonists showed that mu and CB1 receptors mediating inhibition of [3H]glutamate release display a non-additive interaction, whereas these receptors synergistically interact regarding their inhibitory control of [3H]GABA release. Finally, the apparent allosteric interaction between antagonists was also observed regarding the effects of other receptor-selective agonists and antagonists at mu opioid and CB1 cannabinoid receptors (mediating inhibition of NMDA-induced [3H]GABA release) and must therefore be a unique property of the receptors involved. These data suggest the existence of physically associated mu opioid and CB1 cannabinoid receptors, whereby activation of these receptors results in either a non-additive (glutamate release) or a synergistic (GABA release) effect. It is proposed that these allosterically interacting mu and CB1 receptors in the NAc core may represent G-protein coupled heterodimeric receptor complexes.

Animals↗
PubMed2003

Neuroadaptive changes in mesocorticolimbic dopamine and acetylcholine neurons following cocaine or saline self-administration are dependent on pre-existing individual differences.

Previously, we demonstrated that stress-induced self-grooming behaviour in rats predicted an enhanced motivation to self-administer cocaine as determined under a progressive ratio schedule of reinforcement. The enhanced motivation of high grooming (HG) rats was associated with a reduced reactivity of dopaminergic neurons in the medial prefrontal cortex and amygdala, but not nucleus accumbens. In the present study, we studied the effect of cocaine and saline self-administration on these pre-existing differences in neurochemical profile by determining the electrically evoked release of [3H]dopamine and [14C]acetylcholine from superfused slices of the nucleus accumbens shell and core, medial prefrontal cortex and amygdala of HG and low grooming (LG) rats. Although HG and LG rats did not differ in acquisition of cocaine and saline self-administration, both conditions induced substantially different neuroadaptations in these rats. Differences in depolarisation-induced dopamine and acetylcholine release were maintained in the medial prefrontal cortex, emerged in the nucleus accumbens and dissipated in the amygdala. These results indicate that altered reactivity of mesocorticolimbic dopaminergic and cholinergic neurons due to exposure to cocaine and environmental stimuli (saline) is dependent on pre-existing neurochemical differences and displays region-specificity. These pre-existing differences and the cocaine- and environmental-induced neuroadaptations seem to act in concert to produce an enhanced motivational state to self-administer cocaine.

Acetylcholine↗
PubMed2001

A cannabinoid mechanism in relapse to cocaine seeking.

Treatment of cocaine addiction is hampered by high rates of relapse even after prolonged drug abstinence. This relapse to compulsive cocaine use can be triggered by re-exposure to cocaine, by re-exposure to stimuli previously associated with cocaine or by exposure to stress. In laboratory rats, similar events reinstate cocaine seeking after prolonged withdrawal periods, thus providing a model to study neuronal mechanisms underlying the relapse to cocaine. The endocannabinoid system has been implicated in a number of neuropsychiatric conditions, including drug addiction. The active ingredient of marijuana, Delta9-tetrahydrocannabinol, activates the mesolimbic dopamine (DA) reward system and has rewarding effects in preclinical models of drug abuse. We report here that the synthetic cannabinoid agonist, HU210 (ref. 13), provokes relapse to cocaine seeking after prolonged withdrawal periods. Furthermore, the selective CB1 receptor antagonist, SR141716A (ref. 14), attenuates relapse induced by re-exposure to cocaine-associated cues or cocaine itself, but not relapse induced by exposure to stress. These data reveal an important role of the cannabinoid system in the neuronal processes underlying relapse to cocaine seeking, and provide a rationale for the use of cannabinoid receptor antagonists for the prevention of relapse to cocaine use.

Animals↗
PubMed2001

A single administration of interleukin-1 or amphetamine induces long-lasting increases in evoked noradrenaline release in the hypothalamus and sensitization of ACTH and corticosterone responses in rats.

Single administration of the cytokine interleukin-1beta (IL-1) or the psychostimulant amphetamine causes long-term sensitization of the hypothalamus pituitary adrenal (HPA) axis, i.e. enhanced adrenocorticotropine hormone (ACTH) and corticosterone responses weeks later. HPA responses to these stimuli involve activation of hypothalamic corticotropin-releasing hormone (CRH) neurons by noradrenergic projections to the paraventricular nucleus (PVN). In search of the underlying mechanisms, we studied the temporal pattern of HPA sensitization in relation to (1) the reactivity of noradrenergic projections to the PVN and (2) altered secretagogue production in hypothalamic CRH neurons. Single exposure to IL-1 or amphetamine induced cross-sensitization of ACTH and corticosterone responses 11 and 22 days later, but not after 42 days. Amphetamine-induced HPA sensitization was not accompanied by increased costorage of arginine vasopressin (AVP) in CRH terminals, as found previously after IL-1 pretreatment. The reactivity of noradrenergic terminals was assessed by measuring the electrically evoked release of [3H]-noradrenaline from superfused PVN slices. Single administration of amphetamine and IL-1 induced a long-lasting (up to 22 days) increase (up to 165%) of evoked noradrenaline release. This indicates that single exposure to psychostimulants or to cytokines can induce a long-lasting increase in stimulus-secretion coupling in brainstem noradrenergic neurons that innervate the PVN. This common, long-lasting functional change may underlie, at least in part, IL-1- and amphetamine-induced HPA cross-sensitization. In addition, increased AVP signalling by hypothalamic CRH neurons appears to play a role in IL-1-induced, but not in amphetamine-induced, HPA sensitization.

Adrenocorticotropic Hormone↗
PubMed2001

A single exposure to morphine induces long-lasting behavioural and neurochemical sensitization in rats.

Repeated exposure to drugs of abuse causes persistent behavioural sensitization and associated adaptations in striatal neurotransmission, which is thought to play an important role in certain aspects of drug addiction. Remarkably, even a single exposure to psychostimulant drugs such as amphetamine or cocaine can be sufficient to elicit long-lasting sensitization. The present study was designed to evaluate whether long-lasting behavioural and neurochemical sensitization can also be evoked by a single exposure to morphine, an opiate drug of abuse. Rats were pretreated once with morphine (2, 10 or 30 mg/kg). Three weeks later, the locomotor effects of morphine and amphetamine, as well as the electrically evoked release of [3H]dopamine and [14C]acetylcholine from slices of nucleus accumbens and caudate-putamen, was assessed. In morphine-pretreated rats, the psychomotor effects of morphine and amphetamine were sensitized. In addition, the electrically evoked release of [3H]dopamine and [14C]acetylcholine was augmented in slices of nucleus accumbens and caudate-putamen from morphine-pretreated animals. Although the sensitization of the locomotor effect of morphine was less profound than previously observed after repeated intermittent morphine treatment, the enduring behavioural and neurochemical consequences of a single and repeated intermittent morphine treatment appear to be highly comparable. We therefore conclude that a single exposure to morphine induces long-lasting behavioural sensitization and associated neuroadaptations.

Acetylcholine↗
PubMed2000

Synergistically interacting dopamine D1 and NMDA receptors mediate nonvesicular transporter-dependent GABA release from rat striatal medium spiny neurons.

Given the complex interactions between dopamine D1 and glutamate NMDA receptors in the striatum, we investigated the role of these receptors in transporter-mediated GABA release from cultured medium spiny neurons of rat striatum. Like NMDA receptor-mediated [(3)H]-GABA release, that induced by prolonged (20 min) dopamine D1 receptor activation was enhanced on omission of external calcium, was action potential-independent (tetrodotoxin-insensitive), and was diminished by the GABA transporter blocker nipecotic acid, indicating the involvement of transporter-mediated release. Interestingly, lowering the external sodium concentration only reduced the stimulatory effect of NMDA. Blockade of Na(+)/K(+)-ATPase by ouabain enhanced NMDA-induced but abolished dopamine-induced release. Moreover, dopamine appeared to potentiate the effect of NMDA on [(3)H]-GABA release. These effects of dopamine were mimicked by forskolin. mu-Opioid receptor-mediated inhibition of adenylyl cyclase by morphine reduced dopamine- and NMDA-induced release. These results confirm previous studies indicating that NMDA receptor activation causes a slow action potential-independent efflux of GABA by reversal of the sodium-dependent GABA transporter on sodium entry through the NMDA receptor channel. Moreover, our data indicate that activation of G-protein-coupled dopamine D1 receptors also induces a transporter-mediated increase in spontaneous GABA release, but through a different mechanism of action, i.e., through cAMP-dependent inhibition of Na(+)/K(+)-ATPase, inducing accumulation of intracellular sodium, reversal of the GABA carrier, and potentiation of NMDA-induced release. These receptor interactions may play a crucial role in the behavioral activating effects of psychostimulant drugs.

Action Potentials↗
PubMed2000

Dissociable effects of the kappa-opioid receptor agonists bremazocine, U69593, and U50488H on locomotor activity and long-term behavioral sensitization induced by amphetamine and cocaine.

RATIONALE: Mesolimbic dopaminergic neurotransmission plays a critical role in the locomotor effects of psychostimulant drugs, but a general involvement in the induction of long-term psychostimulant sensitization is questionable. By influencing dopaminergic neurotransmission, opioid drugs can alter the behavioral effects of psychostimulants. OBJECTIVES: The effects of the kappa-opioid receptor agonists bremazocine, U69593, and U50488H on the locomotor stimulant and the long-term sensitizing effects of amphetamine and cocaine were investigated in rats. Unlike U69593 and U50488H, bremazocine is also an antagonist at mu- and delta-opioid receptors, as well as an agonist at a subtype of delta-opioid receptors inhibiting dopamine D1 receptor-stimulated adenylate cyclase. METHODS: Bremazocine, U69593, and U50488H were administered prior to amphetamine and cocaine, and locomotor activity was measured. In separate studies, the opioids were co-administered with amphetamine and cocaine for 5 days, and locomotor sensitization was assessed 3 weeks post-treatment. RESULTS: Bremazocine and U69593 attenuated the psychomotor stimulant effects of amphetamine and cocaine. U50488H attenuated the locomotor effect of cocaine and biphasically affected amphetamine-induced locomotion, i.e., suppression followed by stimulation. Bremazocine prevented the development of amphetamine-induced but not cocaine-induced long-term sensitization. Neither U69593 nor U50448H affected the induction of long-term amphetamine or cocaine sensitization. CONCLUSIONS: In agreement with previous studies, the present data suggest that differential mechanisms underlie the acute stimulant versus the long-term sensitizing effects of psychostimulants, and the induction of long-term sensitization by amphetamine versus cocaine. Stimulation of kappa-opioid receptors does not seem to block the induction of long-term psychostimulant sensitization. Thus, bremazocine is likely to block the induction of amphetamine sensitization through a non-kappa-opioid receptor mechanism. We suggest that this effect of bremazocine is the result of its unique agonist action at a subtype of delta-opioid receptors, thereby acting as a functional dopamine D1 receptor antagonist. This would be consistent with the literature showing that the induction of long-term amphetamine sensitization depends on the activation of dopamine D1 receptors. In addition, the present data are in keeping with studies showing that dopamine neurotransmission is not critical for the induction of long-term cocaine sensitization.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1999

A single exposure to amphetamine is sufficient to induce long-term behavioral, neuroendocrine, and neurochemical sensitization in rats.

Repeated treatment with psychostimulant drugs causes long-lasting behavioral sensitization and associated neuroadaptations. Although sensitization induced by a single psychostimulant exposure has also been reported, information on the behavioral and neurochemical consequences of a single psychostimulant exposure is sparse. Therefore, to evaluate whether behavioral sensitization evoked by single and repeated psychostimulant pretreatment regimens represent the same neurobiological phenomenon, the time-dependent expression of behavioral, neurochemical, and neuroendocrine sensitization after a single exposure to amphetamine was investigated in rats. A single exposure to amphetamine (5 mg/kg, i.p.) caused context-independent sensitization of the locomotor effects of amphetamine, which intensified over time. Thus, sensitization to amphetamine was marginal at 3 d after treatment and more evident after 1 week, whereas 3 weeks after treatment, profound sensitization, as well as cross-sensitization, to cocaine was observed. Amphetamine pretreatment caused an increase in the electrically evoked release of [(3)H]dopamine from nucleus accumbens, caudate putamen, and medial prefrontal cortex slices and of [(14)C]acetylcholine from accumbens and caudate slices. The hyperreactivity of dopaminergic nerve terminals appeared to parallel the development of locomotor sensitization, i.e., whereas hyperreactivity of accumbens dopaminergic terminals increased between 3 d and 3 weeks after treatment, the hyperreactivity of medial prefrontal dopaminergic terminals decreased. Pre-exposure to amphetamine also sensitized the hypothalamus-pituitary-adrenal axis response to amphetamine at 1 and 3 weeks, but not at 3 d after treatment. Because these data closely resemble those reported previously for repeated amphetamine pretreatment, it is concluded that a single exposure to amphetamine is sufficient to induce long-term behavioral, neurochemical, and neuroendocrine sensitization in rats.

Acetylcholine↗
PubMed1999

Opposing role of dopamine D1 and D2 receptors in modulation of rat nucleus accumbens noradrenaline release.

The role of dopamine receptors in the modulation of nucleus accumbens noradrenaline release was investigated in superfused rat brain slices. At concentrations of </=1 microM, dopamine enhanced, whereas at higher concentrations dopamine inhibited electrically evoked [3H]noradrenaline release. The D1 receptor agonist SKF-38393 increased, whereas the D2 agonist quinpirole inhibited evoked [3H]noradrenaline release. These effects were attenuated by the D1 antagonist SCH-23390 and the D2 antagonist (-)-sulpiride, respectively, indicating that accumbens noradrenaline release is regulated by stimulatory D1 and inhibitory D2 receptors. Whereas (-)-sulpiride enhanced, SCH-23390 did not reduce evoked accumbens [3H]noradrenaline release, indicating a tonic activation of D2 receptors only. Given the similar apparent affinity of dopamine for D1 and D2 receptors in striatal slices, the lack of tonic D1 receptor activation suggests that D1, unlike D2, receptors are extrasynaptically localized. No dopaminergic modulation of noradrenaline release was observed in rat medial prefrontal cortex or amygdala slices. To examine the regulation of accumbens noradrenaline release under conditions of increased dopaminergic activity, measurements were made using slices of amphetamine-pretreated rats. In these slices, the electrically evoked release of [3H]dopamine and [3H]noradrenaline was enhanced. The increasing effect of (-)-sulpiride on noradrenaline release was augmented, and SCH-23390 almost completely reversed this enhancement of [3H]noradrenaline release. These data suggest that whereas although under a moderate dopaminergic tone, accumbens noradrenaline release is mainly regulated by inhibitory D2 receptors, under circumstances of increased dopaminergic activity, recruitment of extrasynaptic stimulatory D1 receptors contributes to enhancement of noradrenaline release.

Adenosine↗
PubMed1999

Unrestricted free-choice ethanol self-administration in rats causes long-term neuroadaptations in the nucleus accumbens and caudate putamen.

In the present study, the reactivity of striatal dopamine and dopamine-sensitive neurons in super-fused striatal slices of ethanol-experienced rats was compared to that of ethanol-naive rats, 3 weeks after oral ethanol self-administration. During the acquisition phase (17 days), rats were offered increasing concentrations of ethanol (from 2 to 10%, 24 h per day) on an alternate-day schedule in a free choice with water. Following 2 weeks of unrestricted 10% ethanol consumption, the highest and lowest drinkers (representing about 25% of the upper and lower extremes of the total population) were selected. Preliminary experiments revealed that both groups of rats displayed a profound increase in ethanol consumption and preference 3 weeks after cessation of ethanol self-administration (deprivation effect). This deprivation effect was associated with an increase in electrically evoked release of [3H]dopamine from superfused nucleus accumbens slices, whereas the evoked [3H]dopamine release from caudate putamen slices remained unchanged. In slices of the caudate putamen, but not in nucleus accumbens slices, postsynaptic dopamine D1 receptor-stimulated cyclic AMP production was also enhanced. In addition, prior ethanol consumption enhanced the electrically evoked release of [14C]acetylcholine release in both striatal regions. Interestingly, the magnitude of these long-term neuroadaptations correlated with the amount of daily ethanol consumption, i.e. neuronal hyperresponsiveness in the striatum was more profound in the high than in the low ethanol drinkers. These data show for the first time that unrestricted free-choice ethanol consumption in rats is associated with a long-term increase in dopaminergic and cholinergic neurotransmission in the nucleus accumbens and caudate putamen. These (and other) neuroadaptations may underlie the enhanced motivation to self-administer ethanol and the maintenance of ethanol consumption long after deprivation.

Acetylcholine↗
PubMed1999

Bremazocine reduces unrestricted free-choice ethanol self-administration in rats without affecting sucrose preference.

It has been postulated that opioid systems in the brain may play a role in ethanol reinforcement. In this respect, mu- and delta-opioid receptors may mediate the rewarding effects whereas kappa receptors are thought to mediate the aversive effects of opioids. Accordingly, long-acting benzomorphans such as bremazocine, that simultaneously act as mu and delta receptor antagonists and kappa receptor agonists may be particularly effective in reducing ethanol self-administration. Therefore, we studied the effect of bremazocine on oral ethanol self-administration in rats using a paradigm [unrestricted free-choice drinking of 10% (v/v) ethanol], previously shown to cause long-term neuroadaptations in the nucleus accumbens and caudate putamen. Bremazocine (0.1 mg/kg, once daily for five consecutive days) reduced ethanol drinking by about 50% during the active period of the animals, whereas the intake of sucrose (3-10% w/v) was affected neither in naive nor in ethanol-experienced rats. This effect of bremazocine appeared not to be secondary to its acute sedative effect or the slight increase in total fluid consumption. Unlike bremazocine, the selective kappa-opioid receptor agonist U50,488H (10 mg/kg, once daily) inhibited ethanol drinking only during the first of 5 treatment days and the opioid receptor antagonist naltrexone (0.3-10 mg/kg, once daily) only caused a modest (about 20%) suppression of ethanol drinking during the first hours after drug injection. Thus, bremazocine appears to be far more potent than the clinically applied drug naltrexone in this respect. Our data further support the role of opioid receptors in ethanol reinforcement and indicate that long-acting mixed-action opioids such as bremazocine may be useful as adjuvants for the clinical management of ethanol addiction.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1999

Dopaminergic mechanisms mediating the long-term expression of locomotor sensitization following pre-exposure to morphine or amphetamine.

The role of dopaminergic mechanisms in opiate- and psychostimulant-induced long-term locomotor sensitization was investigated. To that aim, rats were behaviourally sensitized with morphine or amphetamine and 3 weeks after cessation of treatment challenged with various direct and indirect dopamine agonists. Both morphine- and amphetamine-pretreated rats displayed sensitization of the locomotor effects of amphetamine, cocaine, and the selective dopamine reuptake inhibitor GBR-12909. Sensitization of the locomotor stimulant effects of the dopamine D2/D3 receptor agonist quinpirole was observed in amphetamine- but not morphine-pretreated rats. In contrast, morphine-, but not amphetamine-pretreated rats appeared hyposensitive to the locomotor inhibitory effects of a low, presumably D2-autoreceptor selective, dose of quinpirole. Neither pretreatment induced sensitization to the dopamine D1/D2 agonist apomorphine or the dopamine D1 agonist SKF-82958. In fact, the locomotor stimulant effects of SKF-82958 appeared to be decreased in animals pre-exposed to amphetamine. These results suggest that functional changes in presynaptic dopamine release mechanisms represent common neuroadaptations involved in the long-term expression of morphine- and amphetamine-induced locomotor sensitization. Presynaptic dopamine D2 and postsynaptic D2 and/or D3 receptors are differentially involved in the expression of morphine- and amphetamine-induced locomotor sensitization. In a parallel study, we report that all of the drugs that elicited sensitized locomotor responses in morphine- or amphetamine-pretreated rats caused reinstatement of previously extinguished heroin- or cocaine-seeking behaviour, respectively. Taken together, these data suggest a marked relationship between drug-seeking behaviour and drug sensitization.

Amphetamine↗
PubMed1999

Dopaminergic mechanisms mediating the incentive to seek cocaine and heroin following long-term withdrawal of IV drug self-administration.

RATIONALE: The neurobiological mechanisms underlying the persistence of drug craving in detoxified addicts are still poorly understood. OBJECTIVE: The present study was designed to evaluate dopaminergic mechanisms in drug-seeking behaviour following long-term (>3 weeks) extinction of IV drug self-administration in rats. METHODS: To that end, we studied the effects of direct and indirect dopamine (DA) agonists on reinstatement of previously extinguished responding for heroin (50 microg/kg per injection; 14-15 daily 3-h sessions) and cocaine (500 microg/kg per injection; 10-11 daily 2-h sessions). RESULTS: In animals with a cocaine history, priming with cocaine, the selective DA reuptake inhibitor GBR-12909 and the DA D2 receptor agonist quinpirole resulted in robust and selective reinstatement of non-reinforced nose poking behaviour in the previously drug-paired hole. In contrast, the D1 agonist SKF-82958 failed to reinstate responding and the non-selective DA agonist apomorphine even suppressed responding in these animals. In heroin-trained rats, heroin and GBR-12909 strongly reinstated responding, whereas all direct DA agonists were ineffective. Again, the two highest doses of apomorphine decreased responding in these animals. In a parallel study, the ability of DA ligands to express behavioural sensitization in animals pretreated with amphetamine or morphine was evaluated. Interestingly, all agonists that reinstated responding in the present study caused expression of locomotor sensitization and vice versa. CONCLUSIONS: The differences between direct and indirect agonists indicate a clear, but complex, involvement of DA in drug-seeking behaviour long after detoxification. Moreover, the results show an important role of D2 receptor activation in the persistence of cocaine- but not heroin-seeking behaviour. Finally, the results from both studies suggest a relationship between drug-induced reinstatement and drug hyperresponsiveness in long-term abstinent rats.

Animals↗
PubMed1999

Stressor- or drug-induced sensitization of the corticosterone response is not critically involved in the long-term expression of behavioural sensitization to amphetamine.

Repeated exposure to drugs of abuse induces long-lasting behavioural sensitization, which is thought to play a role in the persistence of drug-seeking behaviour. Recently, we showed that repeated exposure of rats to cocaine resulted in a long-lasting (weeks) sensitization of the hypothalamus-pituitary-adrenal axis, i.e. hypersecretion of adrenocorticotropic hormone and of the glucocorticoid corticosterone. Moreover, we found that the administration of a glucocorticoid receptor antagonist abolished the expression of psychostimulant-induced behavioural sensitization. In the present study we tested whether stressor- or drug-induced long-term hypersecretion of corticosterone is associated with the long-term expression of behavioural sensitization to psychostimulant drugs. To that end, groups of male Wistar rats were exposed once to interleukin-1beta or to footshocks, treatments that are known to induce long-term sensitization of the hypothalamus-pituitary-adrenal axis, or were treated with amphetamine or morphine, according to protocols known to induce long-lasting behavioural (locomotor) sensitization. Three weeks later, the groups and their controls were challenged with amphetamine or vehicle. Previous exposure to interleukin-1beta or footshocks enhanced adrenocorticotropic hormone and corticosterone responses, but did not affect the long-term locomotor sensitization to amphetamine. Prior amphetamine treatment enhanced the locomotor response and the adrenocorticotropic hormone and corticosterone responses to amphetamine. Prior morphine treatment resulted in long-term locomotor sensitization, whereas the adrenocorticotropic hormone and corticosterone responses to amphetamine were decreased. From these findings and the absence of within-group correlation between corticosterone and locomotor responses in interleukin-1beta and morphine-pretreated rats, we conclude that there is no correlation between sensitization of the corticosterone response and behavioural sensitization to amphetamine. Apparently, sensitization of the corticosterone response is not a prerequisite for the long-term expression of behavioural sensitization, which suggests that drug-induced long-term behavioural sensitization may involve corticosteroid receptor-dependent (central) mechanisms that occur independent of hypothalamus-pituitary-adrenal axis responsiveness.

Adrenocorticotropic Hormone↗
PubMed1999

Lack of cross-sensitization of the locomotor effects of morphine in amphetamine-treated rats.

Repeated exposure to morphine and amphetamine induces long-lasting sensitization of their psychomotor stimulant properties, whereas pretreatment with morphine causes cross-sensitization of the locomotor effects of amphetamine. Here, we investigated whether pre-exposure to amphetamine also results in cross-sensitization to morphine. Rats pretreated with amphetamine (5 x 2.5 mg/kg, i.p.) displayed neither short-term (3 days post-treatment) nor long-term (3 weeks post-treatment) cross-sensitization of the locomotor effects of morphine (2 or 5 mg/kg, s.c.). Two other amphetamine pretreatment protocols (1 x 5 mg/kg, i.p. and 14 x 2.5 mg/kg, i.p.) also failed to induce cross-sensitization to morphine. In contrast, all amphetamine pretreatment regimens induced sensitization of the locomotor effects of amphetamine (1 mg/kg, i.p.) and pretreatment with morphine (14 x 10 mg/kg, s.c.) induced both short- and long-term sensitization of the locomotor effects of both morphine and amphetamine. These data suggest that the expression of sensitization of the locomotor effects of morphine and amphetamine, at least partially, involves distinct neuroadaptive phenomena.

Amphetamine↗
PubMed1998

Infusion of a D-1 receptor agonist into the nucleus accumbens enhances cocaine-induced behavioural sensitization.

The present study was designed to evaluate the effect of dopamine (DA) D-1 receptor activation in the nucleus accumbens (NAC) on the locomotor sensitizing effects of repeated intra-accumbens (intra-NAC) infusions of cocaine. Repeated infusion of cocaine (10 microg/0.5 microl daily for 2 days) resulted in an enhanced locomotor response to a subsequent intra-NAC and systemic (i.p.) challenging dose of the psychostimulant. Pretreatment with the selective D-1 agonist SK&F82958 (1.0 microg) markedly enhanced the sensitizing effects of both intra-NAC and systemic cocaine. The effect of SK&F82958 was completely blocked by systemic administration of the D-1 antagonist SCH23390 (0.1 mg/kg, i.p.). These data give further support to the idea that activation of D-1 receptors plays an important role in the induction of locomotor sensitization and show that the NAC may, in fact, be an anatomical locus of initiation of behavioural sensitization.

Analysis of Variance↗
PubMed1998

MK-801 reinstates drug-seeking behaviour in cocaine-trained rats.

We evaluated the incentive motivational properties of MK-801 by determining its priming effect on drug-seeking behaviour following extinction of cocaine self-administration, an animal model for drug craving. Rats were allowed to self-administrate cocaine (0.5 mg/kg) or saline during 10 daily sessions. MK-801 (0.1-0.25 mg/kg, i.p.) dose-dependently reinstated responding for cocaine following an extinction period of 3 weeks. Responding was selectively enhanced in the previously drug-paired hole and was completely absent in rats with a history of saline self-administration. These data provide evidence for a possible role of NMDA receptors in the incentive motivation underlying cocaine-seeking behaviour. In addition, the ability of MK-801 to elicit drug-seeking behaviour may prove to be a serious drawback for the proposed use of NMDA antagonists in the treatment of drug addiction.

Analysis of Variance↗