The effects of chlorpromazine on psychomotor stimulant self-administration in the Rhesus monkey

Wilson, Marvin C.; Schuster, Charles R.

doi:10.1007/bf00422098

Cited by 176 publications

(58 citation statements)

References 10 publications

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“…This type of comparison is not typically conducted for dopamine agonists. In fact, to control for "drug history" in cocaine substitution studies, many investigators include experimentally-naive subjects that are trained to self-administer cocaine at the start of the study (e.g., Wilson and Schuster 1972;Woolverton et al 1984;Lamb and Griffiths 1990;Katz et al 1992). It has been assumed that drugs that function as reinforcers in substitution paradigms have abuse liability, and this has certainly proven valid for the majority of compounds.…”

Section: Discussionmentioning

confidence: 98%

Self-administration of the dopamine D3 agonist 7-OH-DPAT in rhesus monkeys is modified by prior cocaine exposure

Nader

Mach

1996

Psychopharmacology

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Cocaine self-administration was compared with responding maintained by the dopamine D3 agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) in rhesus monkeys. In the first experiment, monkeys (n = 3) with an extensive cocaine history responded under a fixed-interval (FI) 5-min schedule of IV cocaine (0.03 mg/kg per injection) presentation, during daily 4-h sessions. When responding was stable, dose-response curves were determined for cocaine (0.01-0.3 mg/kg per injection) and 7-OH-DPAT (0.001-0.1 mg/kg per injection); each dose was available for at least five consecutive sessions. When substituted for the baseline dose of cocaine, other doses of cocaine and 7-OH-DPAT maintained rates higher than responding maintained by saline injections, in all monkeys. 7-OH-DPAT maintained response rates equal to or higher than rates of cocaine-maintained responding in all monkeys. In a second experiment, acquisition of 7-OH-DPAT self-administration was evaluated in a group of cocaine-naive monkeys (n = 3). Various doses of 7-OH-DPAT (0.003-0.03 mg/kg per injection) were available under an FI 15-s schedule during daily 4-h sessions. After 10-13 sessions, 7-OH-DPAT self-administration could not be trained in any cocaine-naive monkey. When cocaine was made available to these monkeys, responding was reliably maintained within one to four sessions and the schedule was gradually increased to FI 5-min. After stable responding under an FI 5-min schedule of 0.03 mg/kg per injection cocaine presentation, 7-OH-DPAT (0.01 mg/kg per injection) was again made available to two of the monkeys, and maintained responding at rates higher than saline. To determine better whether a history of responding maintained by another reinforcer would result in high rates of 7-OH-DPAT self-administration, two cocaine-naive monkeys were trained to respond under an FI 5-min schedule of food presentation. Substituting 7-OH-DPAT (0.003-0.03 mg/kg per injection) for food resulted in very low rates of responding. Taken together, these results suggest that despite comparable reinforcing effects in cocaine-substitution studies, 7-OH-DPAT and cocaine differ in their rate of acquisition, perhaps indicating a lower abuse liability for 7-OH-DPAT.

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Section: Discussionmentioning

confidence: 98%

Self-administration of the dopamine D3 agonist 7-OH-DPAT in rhesus monkeys is modified by prior cocaine exposure

Nader

Mach

1996

Psychopharmacology

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“…Dopaminergic antagonists and lesions of dopamine-containing cell bodies attenuate stimulant-induced psychomotor activation, self-administration, and c-fos expression (Schlechter and Butcher, 1972;Wilson and Schuster, 1972;Hollister et al, 1974;Roberts et al, 1977Roberts et al, , 1989Graybiel et al, 1990;Bhat and Baraban, 1993;Cenci and Bjorklund, 1994). Furthermore, HFS of the STN increases the therapeutic efficacy of L-DOPA in patients with Parkinson's disease.…”

Section: Discussionmentioning

confidence: 99%

Subthalamic Nucleus Lesions Enhance the Psychomotor-Activating, Incentive Motivational, and Neurobiological Effects of Cocaine

Uslaner

Yang

Robinson³

2005

J. Neurosci.

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The subthalamic nucleus (STN) is traditionally thought to be involved in motor control, and dysfunction of the STN is thought to contribute to movement disorders. Here, we show that the STN also plays an important role in motivational processes and the response to drugs of abuse. Specifically, bilateral STN lesions produced a dose-dependent increase in the psychomotor-activating effects of cocaine, the rate at which animals acquired cocaine self-administration, and the motivation for cocaine assessed using a progressive ratio schedule. Furthermore, bilateral STN lesions enhanced the ability of cocaine to induce gene expression in the nucleus accumbens and caudate-putamen, two structures known to be involved in mediating the psychomotor-activating and incentive motivational effects of drugs of abuse. These findings suggest that engagement of the STN serves to dampen the psychomotor-activating and incentive motivational effects of drugs of abuse. Thus, the STN may serve as a novel target for therapeutic interventions aimed at treating drug dependence.

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“…Moreover, co caine's acute subjective effects and heart rate increases were greater in polydrug users on methadone main tenance (50 mg/day) than in abstinent opioid abusers (Preston et al 1993) . Preclinical studies of the effects of opioid agonists on cocaine self-administration by monkeys are also inconsistent; both no effect (Stretch 1977) and decreased cocaine self-administration have been reported (Wilson and Schuster 1970;Winger et al 1992) .…”

Section: Discussionmentioning

confidence: 99%

Naltrexone–Buprenorphine Interactions: Effects on Cocaine Self-Administration

Mello

Lukas

Mendelson

et al. 1993

Neuropsychopharmacol

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An opioid mixed agonist-antagonist analgesic, buprenorphine, significantly reduces cocaine self-administration by rhesus monkeys, but the relative contribution of buprenorphine's agonist and antagonist properties to this effect is unclear. This study examined the effects of concurrent treatment with naltrexone, a long-acting mu opioid antagonist, on buprenorphine's effects on cocaine and food self-administration by five rhesus monkeys. Cocaine (0.5 mglkg per injection) and food self-administration (1 gm banana pellet) were maintained on a second order fixed ratio 4 (FR4) variable ratio (VR) 16:5 schedule of reinforcement. Buprenorphine treatment alone (0.40 mglkglday) and in combination with ascending doses of naltrexone (0. OS, 0.10, 0.20, and DAD mglkglday) was compared with naltrexone alone (DAD mglkglday) and saline control treatment. Naltrexone was administered simultaneously or 20 minutes before buprenorphine administration. Each treatment condition was in effect for 10 days.Buprenorphine alone significantly reduced cocaine self-administration by an average of 53% in comparison to the saline treatment baseline (p < .01). When saline

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The effects of chlorpromazine on psychomotor stimulant self-administration in the Rhesus monkey

Cited by 176 publications

References 10 publications

Self-administration of the dopamine D3 agonist 7-OH-DPAT in rhesus monkeys is modified by prior cocaine exposure

Self-administration of the dopamine D3 agonist 7-OH-DPAT in rhesus monkeys is modified by prior cocaine exposure

Subthalamic Nucleus Lesions Enhance the Psychomotor-Activating, Incentive Motivational, and Neurobiological Effects of Cocaine

Naltrexone–Buprenorphine Interactions: Effects on Cocaine Self-Administration

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