Ontogeny of apomorphine-induced stereotypy and its D1 and D2 receptor mediation in rats depleted of dopamine as neonates.
The ontogeny of apomorphine-induced stereotypy in rats treated with 6-OHDA (100 micrograms) or its vehicle on postnatal Day 3 was determined on Days 6, 21, or 60-90. Stereotypic sniffing and mouthing behavior were produced by apomorphine in control and DA-depleted animals as early as Day 6. Animals depleted of DA as neonates exhibited supersensitivity to these behavioral effects from Day 6 into adulthood. The relative contributions of D1 and D2 receptor activation to apomorphine-induced behaviors were determined by measuring the ability of specific D1 or D2 antagonists to block these effects in adults. Blockade of D1 receptors with SCH 23390 or D2 receptors with clebopride suppressed apomorphine-induced stereotypy in both vehicle- and 6-OHDA-treated rats. However, adults depleted of DA as neonates were less sensitive to the DA antagonists than were control rats. These results demonstrate that apomorphine-induced stereotypy is present as early as postnatal Day 6. Rats depleted of DA as neonates continue to exhibit these behaviors, even at lower doses of apomorphine than were necessary in control animals. Finally, coactivation of D1 and D2 receptors appears necessary for apomorphine-induced stereotypy in both groups of rats.
Abrams
D R
DR
Department of Psychology, Ohio State University, Columbus 43210.
Bruno
J P
JP
D000375:Aging / Q000502:physiology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D016627:Oxidopamine / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000502:physiology; D013239:Stereotyped Behavior / Q000187:drug effects* / Q000502:physiology
D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016627:Oxidopamine; D001058:Apomorphine