Differential neurobehavioral deficits induced by apomorphine and its oxidation product, 8-oxo-apomorphine-semiquinone, in rats.
Apomorphine is a potent dopamine receptor agonist, which has been used in the therapy of Parkinson's disease. It has been proposed that apomorphine and other dopamine receptor agonists might induce neurotoxicity mediated by their quinone and semiquinone oxidation derivatives. The aim of the present study was to evaluate the possible neurobehavioral effects of apomorphine and its oxidation derivative, 8-oxo-apomorphine-semiquinone (8-OASQ). Adult female Wistar rats were treated with a systemic injection of apomorphine (0.05 or 0.5 mg/kg) or 8-OASQ (0.05 or 0.5 mg/kg) 20 min before behavioral testing. Apomorphine and 8-OASQ induced differential impairing effects on short- and long-term retention of an inhibitory avoidance task. Apomorphine, but not 8-OASQ, dose-dependently impaired habituation to a novel environment. The memory-impairing effects could not be attributed to reduced nociception or other nonspecific behavioral alterations, since neither apomorphine nor 8-OASQ affected footshock reactivity or behavior during exploration of an open field. The results suggest that oxidation products of dopamine or dopamine receptor agonists might induce cognitive deficits.
Picada
Jaqueline N
JN
GENOTOX-Genotoxicity Laboratory, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), 91501-970, Pôrto Alegre RS, Brazil.
Schröder
Nadja
N
Izquierdo
Ivan
I
Henriques
João Antônio Pêgas
JA
Roesler
Rafael
R
D000818:Animals; D000978:Antiparkinson Agents / Q000378:metabolism / Q000633:toxicity*; D001058:Apomorphine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D018491:Dopamine Agonists / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D010084:Oxidation-Reduction; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
C470323:8-oxo-apomorphine-semiquinone; D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D011809:Quinones; D001058:Apomorphine