Pharmacotherapies for Treatment of Cocaine Abuse:  Preclinical Aspects

Fi, Carroll; Howell, LL; Kuhar, MJ

doi:10.1021/jm9706729

Cited by 232 publications

(276 citation statements)

References 167 publications

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“…Alterations in forebrain serotonin transmission are implicated in both the acute and the enduring psychomotoractivating effects of cocaine (for reviews, Walsh and Cunningham, 1997;Carroll et al, 1999;Weiss et al, 2001;Lima et al, 2003). Thus, the present study determined the relative contribution of the serotonergic projections emanating from the DRN and the MRN to the acute and longterm behavioral and neurochemical consequences of cocaine administration.…”

Section: Discussionmentioning

confidence: 99%

Dissociable Roles for the Dorsal and Median Raphé in the Facilitatory Effect of 5-HT1A Receptor Stimulation upon Cocaine-Induced Locomotion and Sensitization

Szumlinski

Frys

Kalivas

2004

Neuropsychopharmacol

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A distinct role for serotonin transmission from the dorsal and median raphé nuclei (DRN and MRN, respectively) was identified in regulating the behavioral and neurochemical effects of acute and repeated cocaine administration. Serotonin 1A (5-hydroxytryptophan (5-HT)1A) receptors were stimulated by intraraphé microinjection of 8-hydroxy-2-(di-n-propylamino)tetralin (DPAT; 5 or 10 mg) and behavior, as well as extracellular neurotransmitter content in the nucleus accumbens was measured. Pretreatment of the DRN with DPAT caused a sensitization-like potentiation of acute cocaine-induced motor activity and an elevation in extracellular dopamine and glutamate. In contrast, DPAT microinjection into the MRN did not alter acute cocaine-induced motor activity or extracellular levels of dopamine or glutamate. Acutely, DPAT microinjection into either raphé nucleus reduced the basal and acute cocaine-stimulated levels of extracellular serotonin. Pretreatment with DPAT before systemic cocaine administration was continued for 5 days, and 3 weeks after the last injection, all rats were administered a cocaine challenge injection. The sensitized behavioral and neurochemical response produced by repeated cocaine in control subjects was unaffected by the intra-DRN administration of DPAT. However, in animals administered DPAT into the MRN, both the sensitized motor response and the increase in glutamate were augmented, while the sensitized serotonin response was blocked, without altering dopamine sensitization. These data show a differential role for 5-HT1A receptors in the DRN and MRN in the acute and sensitized effects of cocaine. While the DRN is involved in the acute effects of cocaine, neuroadaptations in the MRN may regulate the long-term consequences of repeated cocaine exposure.

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Section: Discussionmentioning

confidence: 99%

Dissociable Roles for the Dorsal and Median Raphé in the Facilitatory Effect of 5-HT1A Receptor Stimulation upon Cocaine-Induced Locomotion and Sensitization

Szumlinski

Frys

Kalivas

2004

Neuropsychopharmacol

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“…As yet, no effective pharmacotherapies have been developed (Mendelson and Mello, 1996;SAMHSA, 2000), but advances in understanding the neurobiological bases of cocaine abuse have led to several pharmacological approaches to treatment. There is considerable evidence that the abuse-related effects of cocaine are mediated by increases in extracellular levels of dopamine in the terminal fields of the mesolimbic dopamine system (Kuhar et al, 1991;Spealman et al, 1992;Carroll et al, 1999;Platt et al, 2002). Accordingly, compounds that modulate dopaminergic activity have been extensively evaluated in preclinical studies as potential treatments for cocaine abuse and dependence (Mello and Negus, 1996;Carroll et al, 1999;Howell and Wilcox, 2001;Platt et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…An alternative approach to the medication-based treatment of cocaine abuse has been to study compounds that can modulate dopaminergic activity indirectly by acting on other receptor systems (Carroll et al, 1999;Bergman et al, 2000;Mello and Negus, 2000). Kappa opioid agonists are one candidate medication for cocaine abuse treatment (Archer et al, 1996;Mello and Negus, 2000).…”

Section: Introductionmentioning

confidence: 99%

Effects of the Mixed Mu/Kappa Opioid Nalbuphine on Cocaine-Induced Changes in Subjective and Cardiovascular Responses in Men

Mello

Mendelson

Sholar

et al. 2004

Neuropsychopharmacol

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Kappa opioid agonists functionally antagonize some abuse-related and locomotor effects of cocaine, and reduce cocaine selfadministration by rhesus monkeys. We compared the cardiovascular and subjective effects of acute doses of the mu/kappa opioid nalbuphine alone (5 mg/70 kg, intravenous (i.v.)), with cocaine alone (0.2 mg/kg, i.v.), and with nalbuphine þ cocaine in combination, under placebo-controlled, double-blind conditions. Subjects met American Psychiatric Association Diagnostic and Statistical Manual (DSM-IV) criteria for current cocaine abuse. Nalbuphine serum levels exceeded 50 ng/ml within 10 min after injection, and cocaine plasma levels exceeded 130 ng/ml within 4 min. Cocaine's pharmacokinetic profile did not change after concurrent nalbuphine administration. The nalbuphine þ cocaine combination was safe and without synergistic effects on heart rate and systolic or diastolic blood pressure. Moreover, the addition of cocaine did not increase the subjective effects of nalbuphine. Visual Analog Scale (VAS) ratings of High, Euphoria, Stimulated, and Good Effect were equivalent after nalbuphine þ cocaine and nalbuphine alone, and both were significantly higher than after cocaine alone (area under the curve analysis) (po0.05-0.01). Peak VAS ratings of High, Stimulated, Good Effect, and Drug Effect were also significantly higher after nalbuphine þ cocaine than after cocaine alone (po0.01). Addiction Research Center Inventory (ARCI) scores were equivalent for nalbuphine þ cocaine and nalbuphine alone, but the PCAG, MBG, and amphetamine scores were significantly higher after both nalbuphine þ cocaine and nalbuphine alone than after cocaine alone (po0.01-0.003). Thus, there were no additive interactions between nalbuphine and cocaine on cardiovascular, subjective, or drug level measures after acute administration.

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“…Thus, increased availability of dopamine for dopamine receptors is believed to mediate most of the reinforcing actions of cocaine, leading to its abuse liability (1,3,23,27). However, cocaine abuse and addiction are processes that go well beyond the pharmacological effects of cocaine on dopamine neurotransmission, so that many other factors, genetic and environmental for example, have been suggested to play a role in the complex of actions that lead from cocaine use to its abuse and addiction (28,29,30,31).…”

Section: Overview On Cocaine Abuse and Addictionmentioning

confidence: 99%

Modulation of the endocannabinoid system: Therapeutic potential against cocaine dependence

Tanda

2007

Pharmacological Research

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Dependence on cocaine is still a main unresolved medical and social concern, and in spite of research efforts, no pharmacological therapy against cocaine dependence is yet available. Recent studies have shown that the endocannabinoid system participates in specific stages and aspects of drug dependence in general, and some of this evidence suggests an involvement of the cannabinoid system in cocaine effects. For example, cocaine administration has been shown to alter brain endocannabinoid levels, and the endocannabinoid system has been involved in long-term modifications of brain processes that might play a role in neuro/behavioral effects of psychostimulant drugs like cocaine. Human studies show that marijuana dependence is frequently associated with cocaine dependence, and that the cannabinoid receptor CNR1 gene polymorphism might be related to cocaine addiction. This article will review the main papers in the field showing how a modulation of different components of the cannabinoid system might interact with some of the neurobiological/behavioral effects of cocaine related to its reinforcing effects, evaluated in preclinical models or in clinical settings. The goal of this review will be to provide insights into the complex picture of cocaine abuse and addiction, and to extrapolate from such endocannabinoid-cocaine interactions useful information to test the therapeutic potential of cannabinoid ligands and endocannabinoid-level enhancers against cocaine dependence for future preclinical/clinical trials.

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Pharmacotherapies for Treatment of Cocaine Abuse: Preclinical Aspects

Cited by 232 publications

References 167 publications

Dissociable Roles for the Dorsal and Median Raphé in the Facilitatory Effect of 5-HT1A Receptor Stimulation upon Cocaine-Induced Locomotion and Sensitization

Dissociable Roles for the Dorsal and Median Raphé in the Facilitatory Effect of 5-HT1A Receptor Stimulation upon Cocaine-Induced Locomotion and Sensitization

Effects of the Mixed Mu/Kappa Opioid Nalbuphine on Cocaine-Induced Changes in Subjective and Cardiovascular Responses in Men

Modulation of the endocannabinoid system: Therapeutic potential against cocaine dependence

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