ISSN:
1432-2072
Keywords:
Antipsychotics
;
S(+)Aporphines
;
Fluphenazine
;
Dopamine
;
Receptors
;
Stereotypy
;
Supersensitivity
;
Tardive dyskinesia
;
Tolerance
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract 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 stereotypy, (+)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 antistereotypy 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. In contrast, the S(+)aporphines had negligible, or minor and transient, effects of a similar kind. These findings support proposals of S(+)aporphines or other D2 partial agonists as potential atypical antipsychotic agents with low risk of inducing long-term adaptive changes in DA receptor sensitivity associated with typical neuroleptic agents.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02244952
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