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Effects of GABAB receptor agonists on cocaine hyperlocomotor and sensitizing effects in rats.

Abstract
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.
AuthorsMałgorzata Frankowska, Ewa Nowak, Małgorzata Filip
JournalPharmacological reports : PR (Pharmacol Rep) 2009 Nov-Dec Vol. 61 Issue 6 Pg. 1042-9 ISSN: 2299-5684 [Electronic] Switzerland
PMID20081239 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • GABA Agonists
  • Organophosphorus Compounds
  • Receptors, GABA-B
  • 3-aminopropyl(methyl)phosphinic acid
  • Baclofen
  • Cocaine
Topics
  • Animals
  • Baclofen (administration & dosage, pharmacology)
  • Behavior, Animal (drug effects)
  • Cocaine (administration & dosage)
  • Dose-Response Relationship, Drug
  • GABA Agonists (administration & dosage, pharmacology)
  • Hyperkinesis (chemically induced)
  • Male
  • Motor Activity (drug effects)
  • Organophosphorus Compounds (administration & dosage, pharmacology)
  • Rats
  • Rats, Wistar
  • Receptors, GABA-B (drug effects, metabolism)

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