Behavioral and neurochemical responses to haloperidol and SCH-23390 in rats treated neonatally or as adults with 6-hydroxydopamine.
Behavioral and neurochemical effects of haloperidol (D2-dopamine antagonist) and SCH-23390 (D1-dopamine antagonist) were examined in unlesioned rats and in rats lesioned with 6-hydroxy-dopamine (6-OHDA) as adults or as neonates. In unlesioned rats, chronic haloperidol treatment (15 days) resulted in an increase in D2-dopamine receptor density, as measured with [3H]spiperone, in the nucleus accumbens and in the caudate-putamen. Rats treated as adults with 6-OHDA responded to chronic haloperidol similarly to controls. However, adult rats treated with 6-OHDA as neonates did not exhibit an increase in [3H]spiperone binding in response to chronic haloperidol treatment. Control and adult 6-OHDA-treated rats given haloperidol exhibited a profound akinesia. In contrast, rats that received 6-OHDA as neonates and were tested as adults did not display a significant behavioral response to haloperidol at doses as high as 2 mg/kg. Results similar to those for haloperidol were also found for SCH-23390. Chronic treatment (15 days) with this D1-dopamine antagonist increased [3H]SCH-23390 binding in the nucleus accumbens and caudate-putamen in unlesioned rats as well as in adult 6-OHDA-treated rats. However, after neonatal 6-OHDA treatment, an elevation in [3H]SCH-23390 binding did not occur after chronic SCH-23390 treatment. SCH-23390 produced akinesia similar to that produced by haloperidol in unlesioned and in adult 6-OHDA-treated rats. In contrast, rats lesioned with 6-OHDA as neonates and tested as adults did not exhibit a significant behavioral response to SCH-23390 under our test conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001552:Benzazepines / Q000378:metabolism / Q000494:pharmacology*; D001679:Biogenic Amines / Q000032:analysis; D001923:Brain Chemistry / Q000187:drug effects; D018492:Dopamine Antagonists; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D006892:Hydroxydopamines / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000032:analysis / Q000187:drug effects*; D013134:Spiperone / Q000378:metabolism
D001552:Benzazepines; D001679:Biogenic Amines; D018492:Dopamine Antagonists; D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D013134:Spiperone; D016627:Oxidopamine; D006220:Haloperidol