The role of D1 and D2 dopamine receptors in oral stereotypy induced by dopaminergic stimulation of the ventrolateral striatum.
Microinjection of amphetamine into the ventrolateral region of the striatum results in compulsive and intense oral stereotypies in the rat. Although these stereotyped behaviors are known to be a direct result of excessive stimulation of the striatal dopamine neurons, the relative roles of the D1 and D2 receptors in oral stereotypies are not clearly understood. It is reported here that microinjection of the selective D1 agonist, SKF 38393 (0, 0.3, 3.0, 30.0 micrograms in 0.5 microliters vehicle) into the ventrolateral striatum resulted in no observable changes in behavior during the 30-min test period. However, it was observed that intense self-biting emerged 3-4 h following injection. Examination of histology from these animals revealed extensive tissue damage and the delayed onset of biting was hypothesized to result from a neurotoxic effect of SKF 38393. Infusion of quinpirole (0, 0.3, 3.0, 30.0 micrograms in 0.5 microliter vehicle), a selective D2 agonist, resulted in a dose-dependent increase in orofacial behaviors such as licking, wood-chip eating, head-down sniffing and mouth movements. Intense oral stereotypies such as biting or gnawing were not observed following treatment with quinpirole. Infusion of the mixed agonist dopamine (0, 2.0, 10.0, 20.0 micrograms in 0.5 microliter vehicle) into the ventrolateral striatum was found to elicit intense oral stereotypy. This behavior consisted almost exclusively of self-biting similar to that observed following amphetamine microinjection into this region. Haloperidol, when given as either a systemic (0.2 mg/kg) or intra-ventrolateral striatum (2.5 micrograms/0.5 microliter) pretreatment, effectively blocked oral stereotypies induced by amphetamine microinjection into the ventrolateral striatum. Pretreatment with either the D1 antagonist SCH 23390 (0, 0.01, 0.1 mg/kg, i.p.) or the D2 antagonist raclopride (0, 0.05, 0.50, 1.0 mg/kg, i.p.) antagonized amphetamine-induced oral stereotypy in a dose-dependent manner. These findings demonstrate that within the striatal site specifically implicated in oral behavior, concurrent stimulation of both receptor subtypes is necessary for the expression of intense oral stereotypies.
Delfs
J M
JM
Department of Psychology, Harvard University, Cambridge, MA 02138.
Kelley
A E
AE
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D019257:Quinpirole; D020891:Raclopride; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects*
D015259:Dopamine Agents; D004873:Ergolines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D019257:Quinpirole; D020891:Raclopride; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D003913:Dextroamphetamine; D004298:Dopamine