NEONATAL EXCITOTOXIC VENTRAL HIPPOCAMPAL DAMAGE ALTERS DOPAMINE RESPONSE TO MILD REPEATED STRESS AND TO CHRONIC HALOPERIDOL

The effects of neonatal excitotoxic ventral hippocampus (VH) lesions o n dopamine release in response to repeated stress (saline injections) and to chronic haloperidol treatment were investigated in Sprague-Dawl ey rats infused with ibotenic acid or vehicle into the VH on day 7 of postnatal life (PD7). Beginning on PD35, lesioned and sham-operated ra ts were injected i.p. with saline (INJ) once daily for 3 weeks or were not treated (NO INJ). Another cohort of rats was given haloperidol (H AL, 0.4 mg/kg, i.p.) or vehicle beginning on PD35 and thereafter once daily for 3 weeks. 3-Methoxytyramine (3-MT) was measured by combined g as chromatography/mass spectrometry in the frontal cortex (FC), nucleu s accumbens (NAcc), and striatum (STR) at PD56 following MAO inhibitio n with pargyline. At baseline (NO INJ), 3-MT was reduced in STR of les ioned rats. Repeated saline injections resulted in a further 3-MT redu ction in STR, FC, and NAcc of lesioned animals, but had no effect in s ham rats. Chronic HAL, compared with vehicle, suppressed locomotor act ivity, and increased 3-MT accumulation in the FC, NAcc, and STR in sha m and lesioned rats. This increase was enhanced in the FC of lesioned rats. These data show that mild repeated stress attenuates dopamine re lease in FC, NAcc, and STR of lesioned rats, while chronic HAL augment s it in FC of lesioned animals versus controls. We conclude that the n eonatal excitotoxic lesion of VH alters the functioning of midbrain do pamine systems during environmental and pharmacological challenge. (C) 1995 Wiley-Liss, Inc.