THE PSYCHOTOMIMETIC DRUGS D-AMPHETAMINE AND PHENCYCLIDINE RELEASE CALCITONIN-GENE-RELATED PEPTIDE IN THE LIMBIC FOREBRAIN OF THE RAT

Calcitonin gene-related peptide (CORP) is the major product of the cal citonin gene in brain and exerts a number of actions in the central ne rvous system (CNS). In particular the finding that CORP affects dopami ne (DA) release and metabolism has raised the possibility that it may play a role in several neuropsychiatric disorders. Consequently, we ha ve here studied the effects of two psychotomimetic drugs, namely, d-am phetamine (AMPH) and phencyclidine (PCP), on CORP concentrations in br ain microdialysates from freely moving rats. The animals were stereota xically implanted with vertical concentric probes in the medial prefro ntal cortex (mPFC), the ventral striatum (vSTR), or the hippocampus; a nd the experiments were performed 48 hr after surgery. The dialysis pr obes were perfused with a modified Ringer's solution at the rate of 5 mu l/min. AMPH 1.5 mg/kg, PCP 2.5 mg/kg, or NaCl 0.9% were injected s. c.; and the perfusates were collected at 60 min intervals before and a fter the injections and used for CORP-like immunoreactivity (-LI) dete rmination by radioimmunoassay (RIA). In separate experiments, KCI (100 mM), veratridine (50 mu M), or tetrodotoxin (2 mu M), were added to t he perfusate and infused in the vSTR. Baseline levels of CORP-LI were detected in dialysates from all three regions. Both AMPH and PCP cause d a significant and sustained increase (maximum about 300%) in CGRP-LI concentrations, in particular from the mPFC and vSTR, while saline ha d no effect. KCI and veratridine also increased CGRP-LI in dialysates during the first posttreatment period, while tetrodotoxin induced a si gnificant but delayed decrease in CGRP-LI levels. Finally, cervical di slocation also elevated CORP-LI in dialysates from the mPFC and the vS TR. Our findings demonstrate that 1) CORP-LI can be measured in vivo i n microdialysates from mPFC, vSTR, and hippocampus; 2) the release in vSTR is action potential-dependent; and 3) systemic administration of AMPH or PCP results in a long-lasting release of CGRP-LI in the mPFC a nd vSTR, thus demonstrating a novel action of these drugs in the brain . Since other studies have shown that major antipsychotic drugs appear to reduce CORP release in brain, our study provides, in principle, su pport for a role of CORP in psychotic disorders. (C) 1996 Wiley-Liss, Inc.