Dopamine depletion in the rostral nucleus accumbens alters the cerebral metabolic response to cocaine in the rat.
The functional consequences of dopamine depletion in the rostral nucleus accumbens were examined using the quantitative 2-[14C]deoxyglucose method for determining rates of local cerebral glucose utilization. Cerebral metabolism was determined in 35 brain structures of Sprague-Dawley rats with unilateral 6-hydroxydopamine or sham lesions of the rostral accumbens. The effect of the lesion was assessed in cocaine-naive animals treated systemically with cocaine or saline. In saline-treated animals, the lesion increased cerebral metabolism in typical basal ganglia regions, such as the globus pallidus and entopeduncular nucleus, as well as portions of the extended amygdala that included the bed nucleus of the stria terminalis and the hypothalamic preoptic area. Cerebral metabolism was affected bilaterally in a subset of all affected structures which demonstrated that the functional consequences of the lesion extended beyond the primary monosynaptic output zones of the rostral accumbens. The lesion also changed the topography of the normal cocaine response such that cocaine effects were blunted in the shell of the nucleus accumbens, globus pallidus and the medial ventral pallidum. Thus, the present study describes functional evidence of the link between the rostral accumbens and the extended amygdala and demonstrates that dopamine in the rostral accumbens plays an important role in the central response to cocaine.
Lyons
D
D
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Winston-Salem, NC 27157, USA.
Porrino
L J
LJ
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D003847:Deoxyglucose / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D007839:Functional Laterality; D005947:Glucose / Q000378:metabolism; D008297:Male; D009498:Neurotoxins; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D016627:Oxidopamine; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley
D018765:Dopamine Uptake Inhibitors; D009498:Neurotoxins; D016627:Oxidopamine; D003847:Deoxyglucose; D003042:Cocaine; D005947:Glucose; D004298:Dopamine