Permanent alteration of central noradrenergic system by prenatally administered amphetamine

Amphetamine-induced psychosis is frequently associated with a chronic, high -dose, daily pattern of amphetamine exposure. In the present study we inves tigate the effects of prenatal exposure to amphetamine during the developme nt of the central noradrenergic (NA) system in adult rats. Pregnant Wistar rats were given 4 mg/kg/day of D-amphetamine (AMPH), subcutaneously, from g estational day 8 to 21. No additional drug treatment was given to the anima ls until the beginning of the experiments, in adult, control and prenatally amphetamine treated rats. Since we study the electrophysiology and neuroch emistry of the central NA system, we investigated the electric activity of locus coeruleus (LC) norepinephrine (NE) neurons and the levels of ME on pr efrontal cortex. What we found, was a decreased number of spontaneously act ive cells in the LC nucleus with a lower pattern of discharge whereas, the basal levels of NE in the prefrontal cortex, was greatly increased. The inc reased cortical NE levels, observed in the present study may account for th e proposed hyperactive NA system being responsible for some psychotic sympt oms observed in paranoid schizophrenia. Besides, our results concerning the permanent alteration observed in the central NA system, in rats prenatally exposed to amphetamine, raise the possibility that this animal model may b e useful to further study the neurobiologic alterations underlying certain clinical features involved in some psychosis such as schizophrenia. (C) 199 9 Elsevier Science B.V. All rights reserved.