Functional imaging and neurochemical correlates of stimulant self-administration in primates

Howell, Leonard L.; Wilcox, Kristin M.

doi:10.1007/s00213-002-1207-y

Cited by 26 publications

(15 citation statements)

References 58 publications

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“…DAT is a major target site of cocaine and is linked to cocaine's acute behavioral effects (e.g., hyperactivity, restlessness, euphoria), which result from enhancement of dopaminergic activity by blocking the presynaptic uptake of dopamine. The relation between DAT occupancy and the reinforcing effects of cocaine and other DAT blockers has also been revealed in PET studies of nonhuman primates (Villemagne et al 1999;Howell and Wilcox 2002). In addition, DAT imaging by PET has been utilized as an objective in vivo means of quantifying the loss of nigrostriatal neurons in Parkinson's disease and a nonhuman primate model of it (Thobois et al 2001;Bohnen and Frey 2003;Nagai et al 2007;Muramatsu et al 2009).…”

Section: Dopamine Transportersmentioning

confidence: 97%

Molecular Brain Imaging of Personality Traits in Nonhuman Primates: A Study of the Common Marmoset

Yokoyama

Onoe

2011

From Genes to Animal Behavior

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Section: Dopamine Transportersmentioning

confidence: 97%

Molecular Brain Imaging of Personality Traits in Nonhuman Primates: A Study of the Common Marmoset

Yokoyama

Onoe

2011

From Genes to Animal Behavior

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“…Preclinical findings indicate that the NA cc , a region at the base of the striatum, is the primary target for the reinforcing effects of drugs of abuse (Howell and Wilcox, 2002;Spanagel and Weiss, 1999). Nevertheless, aggregate findings from PET studies suggest that more information is needed about the relative importance and involvement of the dorsal caudate and putamen in humans (Drevets et al, 2001;Leyton et al, 2002;Martinez et al, 2003).…”

Section: Roi Definitionmentioning

confidence: 99%

Relationships Among Ventral Striatal Dopamine Release, Cortisol Secretion, and Subjective Responses to Amphetamine

Oswald

Wong

McCaul

et al. 2005

Neuropsychopharmacol

296

166

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There is evidence that stress and glucocorticoids alter drug self-administration and mesolimbic dopamine (DA) activity in preclinical models. The primary purpose of this study was to test the hypothesis that glucocorticoids are associated with psychostimulant reinforcement and DA release in humans. In total, 16 healthy adults, ages 18-27 years, underwent two consecutive 90-min PET studies with high specific activity [11 C]raclopride. The first scan was preceded by intravenous saline, and the second by intravenous amphetamine (AMPH 0.3 mg/kg). DA release was defined as the percent change in raclopride binding between the placebo and AMPH scans. Measures of subjective drug effects, plasma cortisol, and growth hormone (GH) were obtained. Findings showed that cortisol levels were positively associated with AMPH-induced DA release in the left ventral striatum (LVS) and the dorsal putamen. Subjects with higher cortisol responses to AMPH also reported more positive subjective drug effects than subjects with lower cortisol responses; no association was observed between cortisol levels and negative drug effects. Higher ratings of positive drug effects were also associated with greater DA release in the LVS, dorsal putamen, and dorsal caudate. A general lack of relationship was observed between GH responses to AMPH and DA release or subjective drug responses. Our findings provide evidence of interrelationships between glucocorticoid levels, subjective responses to IV AMPH, and brain DA release in humans. The results are consistent with those of preclinical studies, suggesting that individual differences in HPA axis function may influence vulnerability to alcohol and drug dependence in humans.

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“…However, plausible alternatives for cocaine dependence may emerge. Some preclinical and clinical data suggest that olanzapine might be efficacious for administration in cocaine dependence (Meil and Schecter, 1997;Bano et al, 2001;Howell and Wilcox, 2002).…”

Section: Treatment With Opioid-stimulant Antagonist-like Combinationmentioning

confidence: 99%

Agonist-Like or Antagonist-Like Treatment for Cocaine Dependence with Methadone for Heroin Dependence: Two Double-Blind Randomized Clinical Trials

Grabowski

Rhoades

Stotts

et al. 2003

Neuropsychopharmacol

173

181

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Concurrent abuse of cocaine and heroin is a common problem. Methadone is effective for opioid dependence. The question arises as to whether combining agonist-like or antagonist-like medication for cocaine with methadone for opioid dependence might be efficacious. Two parallel studies were conducted. One examined sustained release d-amphetamine and the other risperidone for cocaine dependence, each in combination with methadone. In total, 240 subjects (120/study) were recruited, who were both cocaine and heroin dependent and not currently receiving medication. All provided consent. Both studies were carried out for 26 weeks, randomized, double-blind and placebo controlled. Study I compared sustained release d-amphetamine (escalating 15-30 or 30-60 mg) and placebo. Study II examined risperidone (2 or 4 mg) and placebo. All subjects underwent methadone induction and were stabilized at 1.1 mg/kg. Subjects attended clinic twice/week, provided urine samples, obtained medication take-home doses for intervening days, and completed self-report measures. Each had one behavioral therapy session/week. In Study I, reduction in cocaine use was significant for the 30/60 mg dose compared to the 15/30 mg and placebo. Opioid use was reduced in all groups with a trend toward greater reduction in the 30/ 60 mg d-amphetamine group. In Study II, methadone reduced illicit opioid use but cocaine use did not change in the risperidone or placebo groups. There were no adverse medication interactions in either study. The results provide support for the agonist-like (damphetamine) model in cocaine dependence treatment but not for antagonist-like (risperidone) treatment. They coincide with our previous reports of amphetamine or risperidone administered singly in cocaine-dependent individuals.

show abstract

Functional imaging and neurochemical correlates of stimulant self-administration in primates

Abstract: Collectively, in vivo neurochemistry and functional imaging have complemented in vitro approaches and have enhanced our current understanding of the neurobiology of abused stimulants.

Cited by 26 publications

References 58 publications

Molecular Brain Imaging of Personality Traits in Nonhuman Primates: A Study of the Common Marmoset

Molecular Brain Imaging of Personality Traits in Nonhuman Primates: A Study of the Common Marmoset

Relationships Among Ventral Striatal Dopamine Release, Cortisol Secretion, and Subjective Responses to Amphetamine

Agonist-Like or Antagonist-Like Treatment for Cocaine Dependence with Methadone for Heroin Dependence: Two Double-Blind Randomized Clinical Trials

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