WITHDRAWAL FOLLOWING COCAINE SELF-ADMINISTRATION DECREASES REGIONAL CEREBRAL METABOLIC-RATE IN CRITICAL BRAIN REWARD REGIONS

The quantitative [C-14]-2-deoxyglucose autoradiographic method was uti lized to assess regional cerebral metabolic rate for glucose (rCMR(glc )) in rat brain during withdrawal from cocaine self-administration. RC MR(glc) was determined in 62 regions from brains of naive rats which w ere placed into an empty operant chamber for 12 hr continuously, and r ats trained to self-administer cocaine during 3 hr training sessions a nd subsequently placed into the operant chamber for 12 hr continuously with or without access to cocaine. Animals placed into the chamber wi thout access to cocaine were examined 6 hr later, while animals allowe d access to the 12 hr cocaine binge were examined either 6 or 72 hr po st-cocaine. Metabolic activity was reduced during withdrawal in the nu cleus accumbens, olfactory tubercle, islands of Calleja region, basola teral and central amygdaloid nuclei, medial septum, piriform and cingu late cortices, rostral caudatoputamen, entopeduncular nucleus and the adjacent lateral hypothalamus, somatosensory, auditory, and motor cort ices compared to the naive state. These effects were usually more seve re at 72 than at 6 hr after binge exposure, with intermediate values o bserved in cocaine trained animals without binge exposure. The respons e was negatively correlated with the amount of cocaine consumed during binge exposure in the striatum, olfactory tubercle, piriform, cingula te, somatosensory, and motor cortices. Thus, the amount of cocaine con sumed can affect the extent of metabolic depression after sustained dr ug exposure. The pattern of regional effects suggests that mesolimbic and rostral extrapyramidal dopamine terminal regions and certain of th eir efferent pathways are preferentially affected during cocaine withd rawal. The reduction of basal metabolic rate observed in these brain r egions during cocaine withdrawal may become more severe with time desp ite the apparent recovery of certain behavioral-motivational responses .