ANATOMICAL LOCALIZATION OF SKF-38393-INDUCED BEHAVIORS IN RATS USING THE IRREVERSIBLE MONOAMINE RECEPTOR ANTAGONIST EEDQ

This study was designed to localize the population of dopamine D1-like receptors involved in grooming and oral movements elicited by systemi c administration of the D1-selective agonist SKF-38393. Receptors in s pecific dopamine terminal regions were inactivated by intracranial inj ection of the nonselective irreversible antagonist N-ethoxycarbonyl-2- ethoxy-1,2-dihydroquinoline (EEDQ). The effect of these injections on behaviors induced by systemic administration of SKF-38393 (10 mg/kg) w as measured 48 hours later. The specific populations of D1-like recept ors inactivated by the EEDQ injections were identified as a loss of H- 3-SCH-23390 binding in a given region using quantitative autoradiograp hy. EEDQ (1.5 mu g/mu l/side) injected into the nucleus accumbens (NAc ) did not alter SKF-38393-induced behaviors. Similarly, injection of E EDQ into the medial caudate-putamen (CPu) failed to alter these behavi ors. In contrast, EEDQ (0.15-1.5 mu g/mu l/side) injected into the lat eral CPu decreased both SKF-38393-induced grooming and oral movements, with complete blockade of grooming observed at the highest dose. To d etermine whether this effect of EEDQ was due to inactivation of D1-lik e receptors, separate groups of animals were pretreated with SCH-23390 (3 mg/kg, S.C.) 15 min prior to injection with EEDQ. Pretreatment wit h SCH-23390 prevented the disruption of SKF-38393-induced behaviors, a s well as the loss of H-3-SCH-23390-labeled binding sites observed aft er injection of EEDQ into the lateral CPu. EEDQ injections that produc ed disruption of SKF-38393-induced behaviors were associated with a gr eater loss of binding in the lateral CPu relative to other regions exa mined including the NAc, medial CPu, and globus pallidus. Furthermore, EEDQ injections that produced the greatest loss of H-3-SCH-23390 bind ing in the latter three regions did not disrupt SKF-38393-induced beha vior. These results demonstrate that stimulation of D1-like receptors in the lateral CPu is necessary for behaviors induced by systemic admi nistration of SKF-38393. The results also demonstrate the utility of t his ''receptor lesion'' technique to localize receptor-mediated behavi ors. (C) 1995 Wiley-Liss, Inc.