Amphetamine and mCPP Effects on Dopamine and Serotonin Striatalin vivo Microdialysates in an Animal Model of Hyperactivity

Abstract

In the neonatally 6-hydroxydopamine (6-OHDA)-lesioned rat hyperlocomotor activity, first described in the 1970s, was subsequently found to be increased by an additional lesion with 5,7-dihydroxytryptamine (5,7-DHT) (i.c.v.) in adulthood. The latter animal model(i.e., 134 μg 6-OHDA at 3 d postbirth plus 75 μg 5,7-DHT at 10 weeks; desipramine pretreatments) was used in this study, in an attempt to attribute hyperlocomotor attenuation by D,L-amphet-amine sulfate (AMPH) and m-chlorophenylpi-perazine di HCl (mCPP), to specific changes in extraneuronal(i.e., in vivo microdialysate) levels of dopamine (DA) and/or serotonin (5-HT). Despite the 98-99% reduction in striatal tissue content of DA, the baseline striatal microdialysate level of DA was reduced by 50% or less at 14 weeks, versus the intact control group. When challenged with AMPH (0.5 mg/kg), the microdialysate level of DA went either unchanged or was slightly reduced over the next 180 min(i.e., 20 min sampling), while in the vehicle group and 5,7-DHT (alone) lesioned group, the microdialysate level was maximally elevated by ~225% and ~450%, respectively - and over a span of nearly 2 h. Acute challenge with mCPP (1 mg/kg salt form) had little effect on microdialysate levels of DA, DOPAC and 5-HT. Moreover, there was no consistent change in the microdialysate levels of DA, DOPAC, and 5-HT between intact, 5-HT-lesioned rats, and DA-lesioned rats which might reasonably account for an attenuation of hyperlocomotor activity. These findings indicate that there are other important neurochemical changes produced by AMPH-and mCPP-attenuated hyperlocomotor activity, or perhaps a different brain region or multiple brain regional effects are involved in AMPH and mCPP behavioral actions.