Effects of monoamine reuptake inhibitors on
cocaine self-administration in rats

by
Tella SR
Department of Pharmacology,
Georgetown University School of Medicine,
Washington, DC, USA.
Pharmacol Biochem Behav 1995 Aug; 51(4):687-92


ABSTRACT

The objective of this study was to investigate the effects of acute administration of monoamine reuptake inhibitors on cocaine self-administration in rats. Pretreatment with GBR 12909 (1-5.6 mg/kg, IV), a dopamine-selective reuptake inhibitor, produced a dose-dependent and large reduction in the self-administration of cocaine (1 mg/kg/infusion). The 3- and 5.6-mg/kg doses of GBR 12909 produced downward shifts in the dose-response curves for cocaine (0.3-3 mg/kg/infusion) self-administration. Unlike GBR 12909, the norepinephrine-selective reuptake inhibitors, desipramine and nisoxetine, at a 10-mg/kg dose produced small, but significant, reductions in the self-administration of cocaine (1 mg/kg/infusion). The 10-mg/kg dose of fluoxetine, a serotonin-selective reuptake inhibitor, produced a small, but not significant, reduction in the self-administration of cocaine. The 10-mg/kg dose of desipramine, nisoxetine, or fluoxetine produced brief respiratory distress and motor abnormalities immediately following IV injections, thereby suggesting that this dose is close to the toxic range for all three drugs. Desipramine, nisoxetine, or fluoxetine at nontoxic doses of 1 and 3 mg/kg had no significant effects on cocaine self-administration. These data indicate that the acute enhancement of endogenous dopaminergic activity by pretreatment with dopamine reuptake inhibitor reduces the total intake of cocaine, thus supporting the hypothesis that the dopamine is critically involved in the reinforcing properties of cocaine. The data also suggest that the acute enhancements in the endogenous norepinephrine or serotonin systems by nontoxic doses of norepinephrine- or serotonin-selective reuptake inhibitors do not appear to alter the reinforcing properties of cocaine.


Reward
Supercoke
GBR12909
Cocaine mules
Cocaine hotspots
Dopaminergic flies?
Dopaminergic agents
Cocaine immunization
The coke-craving brain
GBR12909 and normal subjects
Freebasing flies go hyperkinetic

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