Effects of naloxone on d-amphetamine- and apomorphine-induced behavior.
The effects of acute naloxone administration on d-amphetamine- and apomorphine-induced behavior were studied. Naloxone, in doses of 0.3-10 mg/kg (s.c.), antagonized the increase in ambulation and rearing induced by 1 mg/kg of d-amphetamine. When the dose of d-amphetamine was increased to 3 mg/kg, naloxone (3 mg/kg) antagonized only the increase in rearing activity. No dose (0.3-10 mg/kg, s.c.) of naloxone significantly affected d-amphetamine- or apomorphine-induced stereotyped activity. Naloxone (3 mg/kg) significantly augmented the apomorphine (1 mg/kg, s.c.)-induced increase in ambulation but attenuated the apomorphine (0.3 mg/kg)-induced increase in rearing activity. Naloxone (3 mg/kg) or apomorphine (0.03 mg/kg) significantly decreased the ambulation and rearing induced by a novel environment. In combination and in these doses, naloxone and apomorphine produced an additive effect on these behaviors. The neurochemical mechanisms by which naloxone affects d-amphetamine- and apomorphine-induced behavior were investigated. Naloxone (10(-6) M) had no significant effect on [3H]spiroperidol binding in either the caudate nucleus or nucleus accumbens except for a modest inhibition (24%) of both the Km and Bmax in the accumbens microsomal fraction. Similarly, naloxone (10(-6) M) had no significant effect on [3H]dopamine(DA) uptake into either brain region nor did naloxone alter the d-amphetamine-inhibition of uptake. Using perfused tissue slices, naloxone (10(-6)-10(-5) M) significantly attenuated the increase in [3H]DA release induced by d-amphetamine (10(-5) M) in both brain regions. Naloxone (1 mg/kg) had no significant effect on DA or dihydroxyphenyl-acetic acid (DOPAC) levels or on the DA/DOPAC ratio in the caudate nucleus or nucleus accumbens. However, naloxone did reverse the marked increases in the DA-DOPAC ratio induced by d-amphetamine (1 mg/kg) in both brain regions.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013134:Spiperone / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects
D015102:3,4-Dihydroxyphenylacetic Acid; D009270:Naloxone; D013134:Spiperone; D001058:Apomorphine; D003913:Dextroamphetamine; D004298:Dopamine