Localization of striatal dopamine receptor function by central injection of an irreversible receptor antagonist.
The stereotypic head-down sniffing response to systemically administered apomorphine (0.65 mumol/kg) was assessed in rats 48 h after the bilateral injection of 0.2-0.5 microliters of the irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (60 micrograms/microliters) into the caudate-putamen and nucleus accumbens. This response was significantly attenuated in animals that had received injections of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline into the anterior/ventral part of the caudate-putamen but not in those that received injections into regions more dorsal/posterior. Animals were killed after apomorphine challenge and the region of dopamine D1 or D2 receptor reduction due to N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline mapped and quantified. This analysis revealed that the dopamine receptors involved in the apomorphine-induced stereotyped head-down sniffing response were located in a discrete region of the ventrolateral caudate-putamen and the dorsolateral nucleus accumbens. Animals that were pretreated with the selective dopamine D2 receptor antagonist raclopride (0 20 mumol/kg, i.p.) 20 min prior to central injection of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline into this area showed a dose-dependent protection of the stereotyped sniffing response to systemic apomorphine 48 h later. This combination of techniques constitutes a novel way to investigate striatal function and the results obtained support the concept of a functional subdivision of both the caudate-putamen and the nucleus accumbens.
Cameron
D L
DL
Department of Clinical Pharmacology School of Medicine, Flinders University of South Australia, Bedford Park.
Crocker
A D
AD
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism* / Q000502:physiology; D018492:Dopamine Antagonists; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism* / Q000502:physiology; D011804:Quinolines / Q000378:metabolism*; D020891:Raclopride; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism / Q000502:physiology*; D012457:Salicylamides / Q000494:pharmacology; D012686:Septal Nuclei / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000187:drug effects*
D018492:Dopamine Antagonists; D011804:Quinolines; D011954:Receptors, Dopamine; D012457:Salicylamides; D020891:Raclopride; C000470:EEDQ; D001058:Apomorphine