Dopamine receptor antagonists prevent the d-amphetamine-induced increase in calcitonin gene-related peptide levels in ventral striatum

Microdialysis in conjunction with radioimmunoassay (RIA) were used to study the effects of acute d-amphetamine or dopamine (DA) receptor antagonists a dministration on extracellular concentrations of calcitonin gene-related pe ptide (CGRP) in the ventral striatum of the rat. One hour after the subcuta neous (s,c.) injection of saline, the DA-D, receptor antagonist SCH 23390 ( 0.3 mg/kg) or the DA-D, receptor antagonist raclopride (1.0 mg/kg), one add itional s,c, injection of saline or d-amphetamine (1,5 mg/kg) was given. Th e dialysates were collected at 60-min intervals; CGRP-like immunoreactiviti es (-LI) were determined by RIA. d-Amphetamine significantly increased extr acellular CGRP-LI concentrations compared to the control animals. Administr ation of either SCH 23390 or raclopride did not significantly affect CGRP-L I concentrations. Pretreatment with either SCH 23390 or raclopride abolishe d the stimulatory effect of d-amphetamine on CGRP-LI levels. The results sh ow that d-amphetamine administration results in an increase in extracellula r concentrations of CGRP in the ventral striatum through a mechanism that a ppears to involve stimulation of either DA-D, or DA-D,,, receptors. The res ults also indicate that changes in dopaminergic neurotransmission affect CO RP outflow in the ventral striatum in a phasic but not tonic manner. (C) 20 01 Wiley-Liss, Inc.