ALTERATIONS IN LOCAL CEREBRAL BLOOD-FLOW IN MATURE RATS FOLLOWING PRENATAL TO COCAINE

Time-mated female Sprague-Dawley rats were injected subcutaneously wit h either 40 mg/kg cocaine-HCl or saline once daily on gestational days 13 through to 16. Local cerebral blood how and glucose use were measu red in the mature male offspring from these darns using the fully quan titative [C-14]2-deoxyglucose and [C-14]iodoantipyrine autoradiographi c techniques, respectively. The effects of the treatment upon the inte grity of central serotonergic terminals was assessed using [H-3]paroxe tine radioligand binding autoradiography. There were no significant ch anges in glucose use in any of the 40 brain areas analysed in this stu dy, and although there was a generalized tendency towards increases, t hese never exceeded +15% of control values. In contrast, significant i ncreases in local cerebral blood flow were measured in more than one-t hird of the areas examined in cocaine-treated rats, ranging from +20% in dorsal raphe nucleus to +95% in some parts of the neocortex. In all but three brain areas, the ratio of cerebral blood flow to metabolic demand was found to increase following cocaine exposure, resetting the relationship from an overall ratio of 1.6 in controls to 2.5 in treat ed rats. This relative hyperaemia, which must result from excessive di latation of the cerebrovascular bed under normal physiological conditi ons, could not be explained by a direct effect of the treatment on ser otonergic constrictor neurons as there was no evidence for any changes in [H-3]paroxetine binding. Whatever the underlying cause, we conclud e that the effects upon cerebrovascular control mechanisms of prenatal exposure to cocaine identified here, might present a further source o f difficulty in the management of ''crack babies''.