Ce. Beyer et Jd. Steketee, Dopamine depletion in the medial prefrontal cortex induces sensitized-likebehavioral and neurochemical responses to cocaine, BRAIN RES, 833(2), 1999, pp. 133-141
It has been postulated that behavioral sensitization to cocaine is associat
ed with an attenuation of cocaine-induced dopamine (DA) transmission in the
medial prefrontal cortex (mPFC). Hence, experiments were designed to exami
ne the effects of chemically-induced cortical DA depletion on the acute beh
avioral and neurochemical responses to cocaine. One week following two bila
teral 6-hydroxydopamine (6-OHDA) injections into the mPFC, animals received
injections of cocaine (7.5, 15 or 30 mg/kg, i.p.) or saline (1 ml/kg, i.p.
) in a randomized fashion with a minimum 3 day intertrial interval. Cocaine
produced a dose-dependent increase in motor activity which was significant
ly enhanced in animals depleted (mean of 76%) of dopamine in the mPFC. Like
wise, 6-OHDA lesions of the mPFC produced a significant enhancement of coca
ine-induced DA transmission in the nucleus accumbens (NAC) as estimated by
in vivo microdialysis. These data indicate a permissive involvement of cort
ical DA in mediating behavioral and neurochemical responses to cocaine, as
well as confirm the ability of the mPFC to influence subcortical structures
in response to an acute injection of cocaine. Collectively, the present fi
ndings suggest that alterations in cortical DA transmission may be a neural
substrate mediating the development of sensitization to cocaine, and thus,
may contribute to the addictive properties of cocaine. (C) 1999 Elsevier S
cience B.V. All rights reserved.