Altered spontaneous behavior and sensitivity to apomorphine in rats following pretreatment with S(+)-aporphines or fluphenazine.
Rats were pretreated for 2 weeks with similarly effective doses of the typical neuroleptic fluphenazine (FPZ) or the experimental weak partial D2 agonists S(+)N-n-propylnorapomorphine (NPA) and S(+)11-hydroxy-N-n-propylnoraporphine (11-OH-NPa). Spontaneous and dopamine (DA) agonist (apomorphine; APO) stimulated stereotyped behaviors or locomotion, and interactions with APO were evaluated over the following 2 weeks. While FPZ induced marked supersensitivity in APO stereotype, (+)NPA showed no significant change, and (+)11-OH-NPa produced only a small, transient increase in response; NPA also lacked a supersensitizing effect on locomotor arousal induced by APO. The time-course of stereotyped responses to APO following pretreatment with FLZ included a marked increase following FPZ that became maximal at day 5 and normalized by day 9; there was a parallel reduction of acute antisteotypy efficacy of FPZ. (+)11-OH-NPa had similar, but much lesser and shorter-lived effects. Spontaneous locomotion was markedly depressed following FPZ, recovered in 1 week, exceeded controls at day 9, and returned to baseline by day 11; (+)11-OH-NPa, again, had similar but smaller effects. Acute effects of FPZ to reduce spontaneous or APO-induced locomotion were greater after FPZ pretreatment and normalized within a week; (+)11-OH-NPa had a similar but smaller effect. Locomotor arousal by APO was altered inconsistently in the week after pretreatment with FPZ or (+)11-OH-NPa. Thus, FPZ appeared to induce tolerance and supersensitivity in central DA systems, most clearly seen following a several-day period to eliminate the drug.(ABSTRACT TRUNCATED AT 250 WORDS)
Campbell
A
A
Consolidated Department of Psychiatry and Neuroscience Program, Harvard Medical School, Boston, MA.
Baldessarini
R J
RJ
Neumeyer
J L
JL
D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000494:pharmacology*; D001060:Aporphines / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005476:Fluphenazine / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects
D001060:Aporphines; D018492:Dopamine Antagonists; C009074:N-n-propylnorapomorphine; D001058:Apomorphine; D005476:Fluphenazine