The secretory trypsin inhibitor like-peptide, PEC-60 increases dopamine D2 receptor agonist induced inhibition of GABA release in the dorsolateral neostriatum of the awake freely moving rat. An in vivo microdialysis study

The effects of local perfusion with the secretory trypsin inhibitor like-peptide, PEC-60 on dopamine and γ-aminobutyric acid (GABA) release in the dorsolateral neostriatum and GABA release in the globus pallidus were studied using in vivo microdialysis in the awake freely moving rat. Local perfusion with PEC-60 (500 nM and 1 μM) increased dopamine release in the dorsolateral neostriatum while the highest (1 μM) concentration of PEC-60 decreased striatal but not pallidal GABA release. An inactive form of the peptide, S-carboxyamidomethylated PEC-60 (1 μM) failed to influence either striatal dopamine and GABA or pallidal GABA release. In addition, when PEC-60, at a dose which did not affect striatal and pallidal GABA release (100 nM), was co-perfused together with the dopamine D2 receptor agonist pergolide (500 nM), a potentiation in the ability of pergolide to reduce GABA release in the dorsolateral neostriatum was observed and this effect was counteracted by co-perfusion with the selective dopamine D2 receptor antagonist raclopride (1 μM). In contrast, the pergolide induced inhibition of striatal dopamine release was unaffected by PEC-60 (100 nM). These data indicate that PEC-60 differentially regulates dopamine and GABA release in the dorsolateral neostriatum by a selective and facilitory interaction with the postsynaptic dopamine D2 receptor possibly involving high-affinity PEC-60 like-peptide binding sites located on local axon collaterals of a discrete subpopulation of efferent GABA neurons and/or on GABA intemeurons.