Injections of baclofen into the ventral medial prefrontal cortex block the initiation, but not the expression, of cocaine sensitization in rats.
BACKGROUND
Increased excitatory output from the medial prefrontal cortex (mPFC) is thought to play a key role in the development of sensitization to cocaine. Gamma-aminobutyric acid (GABA) inhibits this excitatory output.


OBJECTIVE
The present studies were designed to determine the effects of intra-mPFC injections of the GABA(B) agonist baclofen on cocaine-induced motor activity and on the development of sensitization to cocaine.


METHODS
Rats received bilateral cannula implants above the ventral mPFC. Initial studies examined the dose-response effects of injection of baclofen (0.05-0.5 nmol/side) into the mPFC on the acute motor-stimulant response to cocaine (15 mg/kg, i.p.). Additional studies determined whether coadministration of intra-mPFC baclofen (0.5 nmol/side) and systemic cocaine (15 mg/kg, i.p.) could alter the initiation and/or expression of cocaine-induced behavioral sensitization.


RESULTS
Intra-mPFC baclofen dose-dependently blocked cocaine-induced motor activity. In sensitization studies, intra-mPFC baclofen was able to prevent the initiation, but not the expression of cocaine-induced sensitization.


CONCLUSIONS
The data suggest that the ability of GABA to modulate excitatory output from the mPFC may be attenuated in animals sensitized to cocaine.
Steketee
Jeffery D
JD
Department of Pharmacology, University of Tennessee Health Science Center, 874 Union Avenue/Room 115 Crowe, Memphis, TN 38163, USA. jsteketee@utmem.edu
Beyer
Chad E
CE
D000818:Animals; D001418:Baclofen / Q000494:pharmacology* / Q000627:therapeutic use; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000188:drug therapy; D003213:Conditioning, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D003042:Cocaine