Jeffery D Steketee1, Chad E Beyer. 1. Department of Pharmacology, University of Tennessee Health Science Center, 874 Union Avenue/Room 115 Crowe, Memphis, TN 38163, USA. jsteketee@utmem.edu
Abstract
RATIONALE: 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. OBJECTIVES: 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.
RATIONALE: 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. OBJECTIVES: 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: Bradley M T Keegan; Thomas J R Beveridge; Jeffrey J Pezor; Ruoyu Xiao; Tammy Sexton; Steven R Childers; Allyn C Howlett Journal: Neuropharmacology Date: 2015-02-25 Impact factor: 5.250
Authors: Timothy R Rose; Ezequiel Marron Fernandez de Velasco; Baovi N Vo; Megan E Tipps; Kevin Wickman Journal: J Neurosci Date: 2021-01-05 Impact factor: 6.167