Mediation in the nucleus accumbens of the discriminative stimulus produced by cocaine

Wood, Douglas M.; Emmett‐Oglesby, M. W.

doi:10.1016/0091-3057(89)90529-7

Cited by 53 publications

(15 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given recent evidence that cocaine-induced increases in DA overflow are dramatically enhanced after pretreatment with either disulfiram or nepicastat (Devoto et al, 2012(Devoto et al, , 2013, the observed potentiation of cocaine discriminative stimulus effects was not unexpected. The cocaine discriminative stimulus is believed to be largely dependent on cocaine-induced increases of extracellular DA within the NAc, but DA increases within the PFC also contribute to this effect (Wood and Emmett-Oglesby, 1989;Callahan et al, 1997). The results of our drug discrimination data are consistent with this notion.…”

Section: Discussionsupporting

confidence: 81%

Dopamine β-Hydroxylase Inhibitors Enhance the Discriminative Stimulus Effects of Cocaine in Rats

Manvich

DePoy

2013

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Inhibitors of dopamine b-hydroxylase (DBH), the enzyme that converts dopamine (DA) to norepinephrine (NE) in noradrenergic cells, have shown promise for the treatment of cocaine abuse disorders. However, the mechanisms underlying the beneficial effects of these compounds have not been fully elucidated. We used the drug discrimination paradigm to determine the impact of DBH inhibitors on the interoceptive stimulus properties of cocaine. Sprague-Dawley rats were trained to discriminate cocaine (5.6 mg/kg) from saline using a multicomponent, food-reinforced discrimination procedure. On test days, subjects were pretreated with the nonselective DBH inhibitor disulfiram (0-100.0 mg/kg i.p.) or the selective DBH inhibitor nepicastat (0-56.0 mg/kg i.p.) 2 hours prior to a test session either alone or in combination with cumulatively administered cocaine (0-5.6 mg/kg i.p.). Neither disulfiram nor nepicastat substituted for the cocaine stimulus when tested up to doses that nonspecifically reduced responding. However, in combination studies, pretreatment with either disulfiram or nepicastat produced leftward shifts in the cocaine dose-response function and also conferred cocaine-like stimulus effects to the selective NE transporter inhibitor, reboxetine (0.3-5.6 mg/kg i.p.). These results indicate that pharmacological inhibition of DBH does not produce cocaine-like interoceptive stimulus effects alone, but functionally enhances the interoceptive stimulus effects of cocaine, possibly due to facilitated increases in DA released from noradrenergic terminals. These findings suggest that DBH inhibitors have low abuse liability and provide support to clinical reports that some subjective effects produced by cocaine, particularly aversive effects, are enhanced after DBH inhibition.

show abstract

Section: Discussionsupporting

confidence: 81%

Dopamine β-Hydroxylase Inhibitors Enhance the Discriminative Stimulus Effects of Cocaine in Rats

Manvich

DePoy

2013

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…These results are in agreement with other results that indicated mediation in the nucleus accumbens of the discriminative effects of d amphetamine and cocaine (10,11). The doses of d-am phetamine and cocaine administered into the nucleus ac cumbens in the substitution for each drug administered systemically were, respectively, 5 fig and 20 ,ig per rat in the above studies.…”

Section: Discussionsupporting

confidence: 82%

“…Intravenous self-administration of d-amphetamine (6) and cocaine (7 9) was disrupted by blocking DA neu rons or depleting DA in the nucleus accumbens of rats. In drug discrimination studies, d-amphetamine (10) and cocaine (11) administered into the nucleus accumbens of rats substituted for these drugs administered systemically. On the other hand, neither d-amphetamine administered into other areas such as the striatum (10) nor cocaine ad ministered into the medial prefrontal cortex or the stria tum (11) substituted for these drugs administered systemi cally.…”

mentioning

confidence: 99%

Effects of Methamphetamine, Dopamine and Noradrenaline Administered into the Nucleus Accumbens of Rats Discriminating Subcutaneous Methamphetamine

Ando

Miyata

Yanagita

1994

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-Since the nucleus accumbens has been hypothesized to centrally mediate the discriminative effects of psychomotor stimulants, the discriminative effects of methamphetamine (MA) as well as dopa mine (DA) and noradrenaline (NA) were observed by intracerebral administration of these drugs into the nucleus accumbens in rats discriminating subcutaneous MA from saline. These rats were trained and main tained to discriminate between MA at 0.5 mg/kg, s.c. and saline under a fixed ratio 10 schedule for food reinforcement in a 2-lever operant chamber situation. Guide cannulae were implanted bilaterally into the nucleus accumbens. In the substitution tests, the drug was administered into the nucleus accumbens. MA at 10 pg per rat substituted for subcutaneous MA in 4 out of 5 rats but neither DA at 10-40 ug per rat (n=7) nor NA at 10-40 pg per rat (n=4) substituted for subcutaneous MA. On the other hand, the same drugs ad ministered into the nucleus accumbens induced increased spontaneous motor activity as also observed in six other untrained rats. MA, DA or NA alone each at 10 pg per rat increased spontaneous motor activity. The discriminative effects of MA are considered to be mediated in the nucleus accumbens of rats. Although DA or NA alone administered into the nucleus accumbens showed similar increasing motor activity effects as those of MA, the discriminative effects of exogenous DA or NA alone administered into the same brain area were different from those of MA in the present experimental condition.Keywords: Drug discrimination, Nucleus accumbens, Methamphetamine, Dopamine, NoradrenalineStudies on the reinforcing and discriminative effects of drugs in animals provide useful information regarding the abuse liability of drugs. Recent studies have shown the in volvement of the mesolimbic and mesocortical dopamine (DA) system in the reinforcing and discriminative effects of psychomotor stimulants (1 3). For example, rats self administered d-amphetamine directly into the nucleus ac cumbens in the mesolimbic pathway (4) and cocaine into the medial prefrontal cortex in the mesocortical pathway (5). Intravenous self-administration of d-amphetamine (6) and cocaine (7 9) was disrupted by blocking DA neu rons or depleting DA in the nucleus accumbens of rats. In drug discrimination studies, d-amphetamine (10) and cocaine (11) administered into the nucleus accumbens of rats substituted for these drugs administered systemically. On the other hand, neither d-amphetamine administered into other areas such as the striatum (10) nor cocaine ad ministered into the medial prefrontal cortex or the stria tum (11) substituted for these drugs administered systemi cally. Thus, the mediation in the nucleus accumbens of the discriminative effects of psychomotor stimulants is indicated. It was also reported from the studies using the in vivo microdialysis technique that d-amphetamine in creased the synaptic concentration of DA in the nucleus accumbens of rats (12, 13). Furthermore, the DA increase caused by d-amphetamine in this brain ...

show abstract

“…Mesolimbic DA plays a critical role in the discriminativestimulus effects of cocaine (e.g., Wood and Emmett-Oglesby, 1989;Callahan et al, 1997;De La Garza et al, 1998;Filip et al, 2000). In rodents, those effects usually have been investigated in subjects trained with 10 mg/kg cocaine.…”

Section: Discussionmentioning

confidence: 99%

Effects of 4′-Chloro-3α-(diphenylmethoxy)-tropane on Mesostriatal, Mesocortical, and Mesolimbic Dopamine Transmission: Comparison with Effects of Cocaine

Ebbs¹,

Newman²,

Katz³

2005

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Increase in dopamine (DA) neurotransmission resulting from blockade of the DA transporter (DAT) after administration of cocaine is believed to play a major role in mediating its behavioral and reinforcing effects. Since it was hypothesized that drugs that block the DAT have cocaine-like behavioral effects, it was of interest to study in the present article the stimulant effects of cocaine on locomotor activity and on pattern of activation of DA neurotransmission in different DAergic terminal areas in rats and compare these effects with those of 4Ј-chloro-3␣-(diphenylmethoxy)-tropane (4-Cl-BZT), a benztropine analog showing higher affinity for the DAT, but reduced behavioral effects compared with cocaine. Administration of cocaine resulted in a dose-dependent stimulation of locomotor activity and DA neurotransmission in the nucleus accumbens shell and core, dorsal caudate, and in the medial prefrontal cortex (PFCX) measured by microdialysis. At comparable doses, the effects of 4-Cl-BZT on DA levels in all brain areas except the PFCX were generally reduced compared with those of cocaine, as were the effects on locomotor activity. The differences in behavioral effects corresponded generally to differences between the drugs with regard to their stimulation of extracellular DA levels, although the mechanism(s) for the differences in extracellular DA may involve effects mediated by sites other than the DAT or differences in the efficiency of the two drugs in blocking DA uptake. Nonetheless, the present results suggest that the differences in behavioral effects between cocaine and 4-Cl-BZT are related to differences in their patterns of activation of DA transmission.

show abstract

Mediation in the nucleus accumbens of the discriminative stimulus produced by cocaine

Cited by 53 publications

References 17 publications

Dopamine β-Hydroxylase Inhibitors Enhance the Discriminative Stimulus Effects of Cocaine in Rats

Dopamine β-Hydroxylase Inhibitors Enhance the Discriminative Stimulus Effects of Cocaine in Rats

Effects of Methamphetamine, Dopamine and Noradrenaline Administered into the Nucleus Accumbens of Rats Discriminating Subcutaneous Methamphetamine

Effects of 4′-Chloro-3α-(diphenylmethoxy)-tropane on Mesostriatal, Mesocortical, and Mesolimbic Dopamine Transmission: Comparison with Effects of Cocaine

Contact Info

Product

Resources

About