The present study was designed to find out whether pharmacological activation of
GABA(B) receptors played a role in
cocaine sensitization. To this end, male Wistar rats were injected with
baclofen or
3-aminopropyl(methyl)phosphinic acid (SKF 97541), the potent and selective
GABA(B) receptor agonists. The rats, which were repeatedly (for 5 days) administered with
cocaine (10 mg/kg) and then challenged with
cocaine (10 mg/kg) after 5-day withdrawal period, showed significantly higher locomotor hyperactivity in comparison with the effect observed in saline-pretreated and
cocaine challenged rats.
Baclofen (1.25, 2.5 and 5 mg/kg), administered for 5 days prior to
cocaine, dose-dependently attenuated
cocaine sensitization. When injected in the same treatment regimen, SKF 97541 (0.03 mg/kg) reduced the development of
cocaine sensitization. To examine the effects of
baclofen and SKF 97541 on the expression of
cocaine sensitization, the drugs were given acutely before a challenge dose of
cocaine (10 mg/kg) on day 10. Either
baclofen (2.5 and 5 mg/kg) or SKF 97541 (0.1 mg/kg) decreased sensitization to
cocaine. Our findings implicate a role of
GABA(B) receptors in locomotor responses to
cocaine. More specifically, they show that stimulation of
GABA(B) receptors exerted inhibitory actions on acute locomotor responses to
cocaine and on the expression of
cocaine sensitization, what may offer a therapeutic potential of
GABA(B) receptor agonists in the treatment of
cocaine dependence.