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 two families, the D(1)-like (D(1) and D(5) receptors) and D(2)-like (D(2), D(3), and D(4) receptors). Experimental evidence indicates that D(2)-like receptors can 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 investigate this issue, rats were trained using standard operant drug discrimination procedures to discriminate 0.10 mg/kg of the putatively D(3) receptor-preferring agonist R(+)-7-hydroxy-N,N,-di-n-propyl-2-aminotetralin (7-OH-DPAT) from saline. Patterns of generalization to D-amphetamine, AMPT, and SCH 23390 indicated a presynaptic action of 7-OH-DPAT, while apomorphine generalization patterns suggested a postsynaptic action; quinpirole generalization suggested both a pre- and postsynaptic action of 7-OH-DPAT. The ability of spiperone, eticlopride, SCH 23390, and UH 232 to partially antagonize the 7-OH-DPAT stimulus attests to its lack of receptor subtype specificity. These results suggest both pre- and postsynaptic actions of 7-OH-DPAT along with a lack of specificity of the various pharmacological compounds for the D(3) receptor.