Ce. Beyer et Jd. Steketee, Intra-medial prefrontal cortex injection of quinpirole, but not SKF 38393,blocks the acute motor-stimulant response to cocaine in the rat, PSYCHOPHAR, 151(2-3), 2000, pp. 211-218
Rationale: Considerable evidence suggests that the medial prefrontal cortex
(mPFC) is an important region in mediating certain behavioral and neuroche
mical responses to cocaine. However, a role for cortical dopamine (DA) rece
ptor subtypes in modulating these responses has yet to be elucidated. Objec
tives: 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 cannu
lae 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 sid
e) approximately 5 min before peripheral administration of saline or cocain
e (15 mg/kg, i.p.). For dialysis experiments, only the highest dose of quin
pirole was examined. Results: Pretreatment with quinpirole produced a dose-
dependent decrease in cocaine-induced motor activity, with the highest dose
s resulting in a complete abolition of the acute motor-stimulant response t
o cocaine. In contrast, intra-mPFC administration of SKF 38393 was not show
n, at the doses tested, to alter cocaine-induced motor activity. In agreeme
nt with the behavioral effects, intra-mPFC quinpirole injection (5 nmol per
side) significantly blocked cocaine-induced DA overflow in the NAG. Conclu
sions: The results of the present study provide additional support that the
mPFC is a neural substrate through which cocaine, in part, produces its mo
tor-stimulant effects. In addition, these data suggest that modulation of c
ortical DA D2 receptors can block;scute cocaine-induced behavioral (locomot
or activity) and neurochemical (DA concentrations in the NAC) responses in
the rat.