title: Intra-medial prefrontal cortex injection of quinpirole, but not SKF 38393, blocks the acute motor-stimulant response to cocaine in the rat.
abstract: BACKGROUND
  Considerable evidence suggests that the medial prefrontal cortex (mPFC) is an important region in mediating certain behavioral and neurochemical responses to cocaine. However, a role for cortical dopamine (DA) receptor subtypes in modulating these responses has yet to be elucidated.
  
  
  OBJECTIVE
  This study investigated the effects of intra-mPFC administration of DA agonists on the acute motor-stimulant response to cocaine. In addition, in vivo microdialysis techniques were employed to determine the effects of intracortical injection on cocaine-induced extracellular DA concentrations in the nucleus accumbens (NAC).
  
  
  METHODS
  One week following bilateral cannulae implantation over the mPFC and the NAC (for dialysis experiments), male Sprague-Dawley rats received an intra-mPFC injection of saline, the DA D2-like agonist quinpirole (0.015, 0.05, 0.15, 0.5, 1.5, or 5.0 nmol per side) or the partial DA D1-like agonist SKF 38393 (0.5, 1.5, or 5.0 nmol per side) approximately 5 min before peripheral administration of saline or cocaine (15 mg/kg, i.p.). For dialysis experiments, only the highest dose of quinpirole was examined.
  
  
  RESULTS
  Pretreatment with quinpirole produced a dose-dependent decrease in cocaine-induced motor activity, with the highest doses resulting in a complete abolition of the acute motor-stimulant response to cocaine. In contrast, intra-mPFC administration of SKF 38393 was not shown, at the doses tested, to alter cocaine-induced motor activity. In agreement with the behavioral effects, intra-mPFC quinpirole injection (5 nmol per side) significantly blocked cocaine-induced DA overflow in the NAC.
  
  
  CONCLUSIONS
  The results of the present study provide additional support that the mPFC is a neural substrate through which cocaine, in part, produces its motor-stimulant effects. In addition, these data suggest that modulation of cortical DA D2 receptors can block acute cocaine-induced behavioral (locomotor activity) and neurochemical (DA concentrations in the NAC) responses in the rat.
authors.affiliation: Department of Pharmacology and Therapeutics and School of Graduate Studies, Louisiana State University Health Sciences Center, Shreveport 71130-3932, USA. cbeyer@lsumc.edu
authors.forename: C E
authors.initials: CE
authors.lastname: Beyer
authors.forename: J D
authors.initials: JD
authors.lastname: Steketee
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000033:anatomy & histology / Q000502:physiology*; D019257:Quinpirole / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D003042:Cocaine