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 investigate the effects of prenatal exposure to amphetamine during the development of the central noradrenergic (NA) system in adult rats. Pregnant Wistar rats were given 4 mg/kg/day of d-amphetamine (AMPH), subcutaneously, from gestational day 8 to 21. No additional drug treatment was given to the animals until the beginning of the experiments, in adult, control and prenatally amphetamine treated rats. Since we study the electrophysiology and neurochemistry of the central NA system, we investigated the electric activity of locus coeruleus (LC) norepinephrine (NE) neurons and the levels of NE on prefrontal cortex. What we found, was a decreased number of spontaneously active 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 increased cortical NE levels, observed in the present study may account for the proposed hyperactive NA system being responsible for some psychotic symptoms 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 be useful to further study the neurobiologic alterations underlying certain clinical features involved in some psychosis such as schizophrenia.
Nasif
F J
FJ
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5000, Córdoba, Argentina.
Cuadra
G R
GR
Ramirez
O A
OA
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000494:pharmacology; D003913:Dextroamphetamine / Q000008:administration & dosage* / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D008125:Locus Coeruleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar
D000697:Central Nervous System Stimulants; D003913:Dextroamphetamine; D009638:Norepinephrine