THE SECRETORY TRYPSIN-INHIBITOR LIKE-PEPTIDE, PEC-60 INCREASES DOPAMINE D-2 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 li ke-peptide, PEC-60 on dopamine and gamma-aminobutyric acid (GABA) rele ase in the dorsolateral neostriatum and GABA release in the globus pal lidus were studied using in vivo microdialysis in the awake freely mov ing rat. Local perfusion with PEC-60 (500 nM and 1 mu M) increased dop amine release in the dorsolateral neostriatum while the highest (1 mu M) concentration of PEC-60 decreased striatal but not pallidal GABA re lease. An inactive form of the peptide, S-carboxyamidomethylated PEC-6 0 (1 mu M) failed to influence either striatal dopamine and GABA or pa llidal GABA release. In addition, when PEC-60, at a dose which did not affect striatal and pallidal GABA release (100 nM), was co-perfused t ogether with the dopamine D-2 receptor agonist pergolide (500 nM), a p otentiation 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 D-2 receptor antagonist r aclopride (1 mu M). In contrast, the pergolide induced inhibition of s triatal dopamine release was unaffected by PEC-60 (100 nM). These data indicate that PEC-60 differentially regulates dopamine and GABA relea se in the dorsolateral neostriatum by a selective and facilitory inter action with the postsynaptic dopamine D-2 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/o r on GABA interneurons.