Critical role of α1‐adrenergic receptors in acute and sensitized locomotor effects of D‐amphetamine, cocaine, and GBR 12783: Influence of preexposure conditions and pharmacological characteristics

Abstract

AbstractPsychostimulant‐induced locomotor hyperactivity is commonly associated with an inhibition of dopamine reuptake. However, a physiological coupling between noradrenergic and dopaminergic neurons occurring through the stimulation of α1‐adrenergic receptors has recently been proposed. This possibility was tested on locomotor responses induced either by D‐amphetamine and cocaine, which both interfere with noradrenergic and dopaminergic transmissions, or by GBR 12783, a specific dopamine reuptake inhibitor. In an attempt to control the effects of stress and novelty on noradrenergic neurons activity, rats were submitted to habituation procedures consisting of either a 15‐h period of habituation to the experimental environment (“long‐habituation”) or to repeated exposure to intraperitoneal saline injections for 3 consecutive days (“three‐session”). Three‐session‐exposed animals exhibited a pronounced locomotor reactivity to saline injection which did not occur after noradrenergic depletion, clonidine (20 μg/kg) or prazosin (0.5 mg/kg) pretreatments, or in long‐habituation‐preexposed animals. Cocaine and GBR 12783 locomotor hyperactivities were doubled in three‐session vs. long‐habituation‐preexposed rats, whereas D‐amphetamine responses were similar in both conditions. Prazosin (0.5 mg/kg) pretreatment reduced the acute locomotor effects of the three psychostimulants in both procedures and blocked the behavioral sensitization induced by repeated injections of D‐amphetamine (0.75 mg/kg) or cocaine (5 mg/kg). GBR 12783 (5 mg/kg) failed to induce significant behavioral sensitization. In addition to their role in the acute and sensitized locomotor responses to psychostimulants possessing different pharmacological characteristics, α1‐adrenergic receptors are involved in animal reactivity to previously experimented procedures. This suggests an implication of noradrenergic neurons in the vulnerability to psychostimulants. Synapse 43:51–61, 2002. © 2001 Wiley‐Liss, Inc.