Alterations in local cerebral blood flow in mature rats following prenatal exposure to cocaine.
Time-mated female Sprague-Dawley rats were injected subcutaneously with either 40 mg/kg cocaine-HCl or saline once daily on gestational days 13 through to 16. Local cerebral blood flow and glucose use were measured in the mature male offspring from these dams using the fully quantitative [14C]2-deoxyglucose and [14C]iodoantipyrine autoradiographic techniques, respectively. The effects of the treatment upon the integrity of central serotonergic terminals was assessed using [3H]paroxetine radioligand binding autoradiography. There were no significant changes in glucose use in any of the 40 brain areas analysed in this study, and although there was a generalized tendency towards increases, these never exceeded +15% of control values. In contrast, significant increases in local cerebral blood flow were measured in more than one-third 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 treated rats. This relative hyperaemia, which must result from excessive dilatation of the cerebrovascular bed under normal physiological conditions, could not be explained by a direct effect of the treatment on serotonergic constrictor neurons as there was no evidence for any changes in [3H]paroxetine binding. Whatever the underlying cause, we conclude that the effects upon cerebrovascular control mechanisms of prenatal exposure to cocaine identified here, might present a further source of difficulty in the management of "crack babies".
Kelly
P A
PA
Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital, U.K.
Ritchie
I M
IM
Sharkey
J
J
McBean
D E
DE
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D001923:Brain Chemistry / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D008297:Male; D017374:Paroxetine; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D017374:Paroxetine; D003042:Cocaine; D005947:Glucose