Effects of intravenous cocaine are partially attenuated by haloperidol

Sherer, Michael A.; Kumor, Karen M.; Jaffe, Jerome H.

doi:10.1016/0165-1781(89)90127-3

Cited by 96 publications

(51 citation statements)

References 20 publications

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“…In studies with humans, the effects of D2 antagonists on psychostimulant reward have been inconsistent. Some studies have found no effect (eg Wachtel et al, 2002); others have found decreased psychostimulant reward (eg Gunne et al, 1972;Jonsson, 1972;Sherer et al, 1989); and one study has found increased psychostimulant reward (Brauer and de Wit, 1996). In their review of the psychostimulant literature, discuss the seeming lack of correspondence between the animal and human research in terms of functional dosing and a variety of methodological differences.…”

Section: Discussionmentioning

confidence: 99%

A D2 Antagonist Enhances the Rewarding and Priming Effects of a Gambling Episode in Pathological Gamblers

Zack

Poulos

2007

Neuropsychopharmacol

155

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Previous research indicated shared neurochemical substrates for gambling and psychostimulant reward. This suggests that dopamine substrates may directly govern the reinforcement process in pathological gambling. To investigate this issue, the present study assessed the effects of the relatively selective dopamine D2 antagonist, haloperidol (3 mg, oral) on responses to actual gambling (15 min on a slot machine) in 20 non-comorbid pathological gamblers and 18 non-gambler controls in a placebo-controlled, double-blind, counterbalanced design. In gamblers, haloperidol significantly increased self-reported rewarding effects of gambling, post-game priming of desire to gamble, facilitation of reading speed to Gambling words, and gambling-induced elevation in blood pressure. In controls, haloperidol augmented gambling-induced elevation in blood pressure, but had no effect on other indices. The findings provide direct experimental evidence that the D2 substrate modulates gambling reinforcement in pathological gamblers.

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Section: Discussionmentioning

confidence: 99%

A D2 Antagonist Enhances the Rewarding and Priming Effects of a Gambling Episode in Pathological Gamblers

Zack

Poulos

2007

Neuropsychopharmacol

155

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“…For example, the euphoria induced by cocaine in experienced users is resistant to DA receptor blockade (Sherer et al, 1989), and mice lacking the DA transporter show both self-administration behavior and conditioned place preference to cocaine (Rocha et al, 1998;Sora et al, 1998). It is interesting, therefore, that iontophoresis of cocaine in alert rats inhibits striatal neurons, but unlike amphetamine iontophoresis, this inhibitory response is not blocked by DA receptor antagonists .…”

Section: Striatal Neuronal Changes Induced By Cocainementioning

confidence: 99%

Behavioral Electrophysiology of Psychostimulants

Rebec

2006

Neuropsychopharmacol

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The motor-activating effects of amphetamine and other psychostimulants such as cocaine depend on an increase in dopamine (DA) transmission in the striatum, a key component of the basal ganglia and the forebrain motive circuit. This review focuses on research aimed at using electrophysiological techniquesFincluding extracellular unit recording and iontophoresisFin alert, fully functioning animals to understand how these drugs alter striatal neuronal processing under behaviorally relevant conditions. The data indicate that DA works in conjunction with glutamate (GLU), an excitatory amino acid, to enhance the signal-to-noise ratio of afferent information. This DA-GLU interaction appears to play a critical role in the amphetamine-induced activation of striatal neurons. The pattern of striatal activation, moreover, changes as the behavioral response changes from unfocused locomotion to highly focused, stereotyped behavior, but interestingly, the striatal response pattern is not reflected in substantia nigra reticulata, a primary target of striatal efferents. Although cocaine also activates striatal neurons during behavior, the underlying mechanisms appear to be complicated by factors unique to this drug and deserve further evaluation. Collectively, these findings provide unique insight into the neuronal processes by which the striatum participates in psychostimulant-induced motor behavior.

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“…In light of the important role of the mesolimbic dopamine (DA) system in drug abuse (Wise, 2005), much attention has focused on various DA receptor antagonists as potential treatments (Rothman and Glowa, 1995;Platt et al, 2002). However, clinical trials with D 1 or D 2 receptor antagonists for cocaine addiction have failed due to either ineffectiveness, surmountability by increased drug intake, and/or unfavorable side-effects such as dysphoria, extrapyramidal movements or inhibition of natural reward (Sherer et al, 1989;Nann-Vernotica et al, 2001;Haney et al, 2001;Newton et al, 2001; see reviews by Platt et al, 2002;Gorelick et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Levo-tetrahydropalmatine inhibits cocaine's rewarding effects: Experiments with self-administration and brain-stimulation reward in rats

Zheng

et al. 2007

Neuropharmacology

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It was recently reported that levo-tetrahydropalmatine (l-THP), a dopamine (DA) D 1 and D 2 receptor antagonist purified from the Chinese herb Stephanie, appears to be effective in attenuating cocaine self-administration, cocaine-triggered reinstatement and cocaine-induced conditioned place preference in preclinical animal models. The present study was designed to contrast l-THP's effects on cocaine self-administration under fixed-ratio (FR) and progressive-ratio (PR) reinforcement, and to study l-THP's effects on cocaine-enhanced brain stimulation reward (BSR). Systemic administration of l-THP produced dose-dependent, biphasic effects, i.e., low-to-moderate doses (1, 3, 10 mg/kg) increased, while a high dose (20 mg/kg) inhibited cocaine self-administration behavior under FR2 reinforcement. The increased cocaine self-administration is likely a compensatory response to a reduction in cocaine's rewarding effects, because the same low doses of l-THP dosedependently attenuated cocaine self-administration under PR reinforcement and also attenuated cocaine-enhanced BSR. These attenuations of PR cocaine self-administration and cocaine-enhanced BSR are unlikely due to l-THP-induced sedation or locomotor inhibition, because only 10 mg/kg, but not 1-3 mg/kg of l-THP inhibited locomotion, sucrose self-administration and asymptotic operant performance in the BSR paradigm. In vivo microdialysis demonstrated that l-THP slightly elevates extracellular nucleus accumbens DA by itself, but dose-dependently potentiates cocaine-augmented DA, suggesting that a postsynaptic, rather than presynaptic, DA receptor antagonism underlies l-THP's actions on cocaine reward. Together, the present data, combined with previous findings, support the potential use of l-THP for treatment of cocaine addiction.

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Effects of intravenous cocaine are partially attenuated by haloperidol

Cited by 96 publications

References 20 publications

A D2 Antagonist Enhances the Rewarding and Priming Effects of a Gambling Episode in Pathological Gamblers

A D2 Antagonist Enhances the Rewarding and Priming Effects of a Gambling Episode in Pathological Gamblers

Behavioral Electrophysiology of Psychostimulants

Levo-tetrahydropalmatine inhibits cocaine's rewarding effects: Experiments with self-administration and brain-stimulation reward in rats

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