Apomorphine-induced inhibition of neostriatal activity is enhanced by lesions induced by 6-hydroxydopamine but not by long-term administration of amphetamine.
Single-unit activity was recorded in the neostriatum of locally-anesthetized, immobilized rats which had received either a unilateral injection of 6-hydroxydopamine (6-OHDA) into the nigro-neostriatal dopamine pathway, or repeated injections (twice daily for 6 days) of saline, 1.0, 5.0 or 10.0 mg/kg (+)-amphetamine. A staircase regimen of apomorphine was administered intravenously to each rat to determine if the long-term administration of amphetamine changed the sensitivity of postsynaptic dopamine receptors in a way comparable to that produced by 6-hydroxydopamine. In all groups, the most frequent response to apomorphine was inhibition of neostriatal activity. In saline-treated rats, most units were moderately excited by small doses of apomorphine (0.0025-0.02 mg/kg) and then inhibited by doses exceeding 0.04 mg/kg. In rats with lesions induced by 6-hydroxydopamine, apomorphine caused significantly more inhibition than in saline-treated animals. By contrast, neuronal responses in amphetamine-treated rats were not significantly different from those of saline controls. These results indicate that the long-term administration of amphetamine produces an augmentation of behavior by some mechanism other than an increase in the sensitivity of postsynaptic dopamine receptors.
D000200:Action Potentials / Q000187:drug effects; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000187:drug effects / Q000502:physiology*; D006892:Hydroxydopamines / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000502:physiology; D016627:Oxidopamine; D011699:Putamen / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology
D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D017981:Receptors, Neurotransmitter; D016627:Oxidopamine; D000661:Amphetamine; D001058:Apomorphine