title: Injections of baclofen into the ventral medial prefrontal cortex block the initiation, but not the expression, of cocaine sensitization in rats.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Tennessee Health Science Center, 874 Union Avenue/Room 115 Crowe, Memphis, TN 38163, USA. jsteketee@utmem.edu
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Steketee
authors.forename: Chad E
authors.initials: CE
authors.lastname: Beyer
mesh_terms: 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
chemical_list: D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D003042:Cocaine