Original Investigation

Psychopharmacology

, Volume 169, Issue 2, pp 176-185

On the role of noradrenaline in psychostimulant-induced psychomotor activity and sensitization

  • Louk J. M. J. VanderschurenAffiliated withDrug Abuse Program, Department of Medical Pharmacology, Research Institute Neurosciences VU, VU Medical Center Email author 
  • , Patricia BeemsterAffiliated withDrug Abuse Program, Department of Medical Pharmacology, Research Institute Neurosciences VU, VU Medical Center
  • , Anton N. M. SchoffelmeerAffiliated withDrug Abuse Program, Department of Medical Pharmacology, Research Institute Neurosciences VU, VU Medical Center

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Abstract

Rationale

Psychostimulant drugs exert their behavioral effects primarily through enhancement of monoaminergic neurotransmission. Augmented dopamine activity is thought to play a critical role in the psychomotor stimulant effects of amphetamine and cocaine, as well as in the development of long-term behavioral sensitization evoked by repeated exposure to amphetamine. However, despite the fact that brain dopamine and noradrenaline systems are closely interconnected, the extent to which noradrenergic transmission contributes to these behavioral effects of psychostimulants is a relatively unexplored issue.

Objectives

By inhibiting noradrenergic neurotransmission with the α2-adrenoceptor agonist clonidine, the α1-antagonist prazosin and the β-antagonist propranolol, we investigated the involvement of noradrenaline neurotransmission in the psychomotor stimulant and long-term sensitizing effects of d-amphetamine and cocaine in rats.

Methods

Clonidine (0.003–0.1 mg/kg), prazosin (0.1–3.0 mg/kg) and propranolol (1.0–3.0 mg/kg) were administered prior to d-amphetamine (1.0 mg/kg), cocaine (15 mg/kg) or apomorphine (1.0 mg/kg) and psychomotor activity was measured. In separate studies, clonidine (0.03 mg/kg), prazosin (1.0 mg/kg) or propranolol (3.0 mg/kg) were co-administered with d-amphetamine (2.5 mg/kg) or cocaine (30 mg/kg) for 5 days, and locomotor sensitization was assessed 3 weeks post-treatment.

Results

The psychomotor stimulant effect of d-amphetamine, but not that of cocaine or apomorphine, was dose-dependently inhibited by clonidine and prazosin, and enhanced by propranolol. Clonidine, prazosin, and propranolol did not influence the induction of sensitization by amphetamine or cocaine.

Conclusions

Enhancement of synaptic noradrenaline concentrations contributes to the psychomotor stimulant effect of d-amphetamine, but not cocaine or apomorphine. In addition, noradrenergic neurotransmission is not critically involved in the induction of psychostimulant sensitization.

Keywords

Amphetamine Apomorphine Cocaine α-Adrenoceptors β-Adrenoceptors Locomotor activity Behavioral sensitization Clonidine Prazosin Propranolol