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 systemic administration of the D1-selective agonist SKF-38393. Receptors in specific dopamine terminal regions were inactivated by intracranial injection 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) was measured 48 hours later. The specific populations of D1-like receptors inactivated by the EEDQ injections were identified as a loss of 3H-SCH-23390 binding in a given region using quantitative autoradiography. EEDQ (1.5 micrograms/microliters/side) injected into the nucleus accumbens (NAc) did not alter SKF-38393-induced behaviors. Similarly, injection of EEDQ into the medial caudate-putamen (CPu) failed to alter these behaviors. In contrast, EEDQ (0.15-1.5 micrograms/microliters/side) injected into the lateral CPu decreased both SKF-38393-induced grooming and oral movements, with complete blockade of grooming observed at the highest dose. To determine whether this effect of EEDQ was due to inactivation of D1-like receptors, separate groups of animals were pretreated with SCH-23390 (3 mg/kg, S.C.) 15 min prior to injection with EEDQ. Pretreatment with SCH-23390 prevented the disruption of SKF-38393-induced behaviors, as well as the loss of 3H-SCH-23390-labeled binding sites observed after injection of EEDQ into the lateral CPu. EEDQ injections that produced disruption of SKF-38393-induced behaviors were associated with a greater loss of binding in the lateral CPu relative to other regions examined including the NAc, medial CPu, and globus pallidus. Furthermore, EEDQ injections that produced the greatest loss of 3H-SCH-23390 binding in the latter three regions did not disrupt SKF-38393-induced behavior. These results demonstrate that stimulation of D1-like receptors in the lateral CPu is necessary for behaviors induced by systemic administration of SKF-38393. The results also demonstrate the utility of this "receptor lesion" technique to localize receptor-mediated behaviors.
Neisewander
J L
JL
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Ong
A
A
McGonigle
P
P
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal; D002352:Carrier Proteins; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D006120:Grooming; D008297:Male; D009714:Nucleus Accumbens; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology*
D002352:Carrier Proteins; D018492:Dopamine Antagonists; D011804:Quinolines; D017447:Receptors, Dopamine D1; C000470:EEDQ; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine