Stimulus properties of 7-OH-DPAT versus auto- and postsynaptic receptor-specific doses of quinpirole

The five types of dopamine (DA) receptor subtypes have been grouped into tw o families, the D-1-like (D-1 and D-5 receptors) and D-2-like (D-2, D-3, an d D-4 receptors). Experimental evidence indicates that D-2-like receptors c an be located either presynaptically, where they modulate the synthesis and release of DA, or postsynaptically. Controversy exists, however, over the precise location and role of the D-3 subtype of DA. receptor. To investigat e this issue, rats were trained using standard operant drug discrimination procedures to discriminate 0.10 mg/kg of the putatively D-3 receptor-prefer ring agonist R(+)-7-hydroxy-N,N,-di-n-propyl-2-aminotetralin (7-OH-DPAT) fr om saline. Patterns of generalization to D-amphetamine, AMPT, and SCH 23390 indicated a presynaptic action of 7-OH-DPAT, while apomorphine generalizat ion patterns suggested a postsynaptic action; quinpirole generalization sug gested both a pre- and postsynaptic action of 7-OH-DPAT. The ability of spi perone, eticlopride, SCH 23390, and UH 232 to partially antagonize the 7-OH -DPAT stimulus attests to its lack of receptor subtype specificity. These r esults suggest both pre- and postsynaptic actions of 7-OK-DPAT along with a lack of specificity of the various pharmacological compounds for the D-3 r eceptor. (C) 2001 Elsevier Science Inc. All rights reserved.