Activation of striatal neurons by dexamphetamine is antagonized by degeneration of striatal dopaminergic terminals.
Unilateral degeneration of nigrostriatal dopaminergic terminals by the intranigral infusion of 6-OHDA produced a decrease in spontaneous multiple unit activity (MUA) in both the ipsilateral and contralateral striata of freely moving rats. Nigral lesions also attenuated the dexamphetamine-induced increase in MUA in the ipsilateral but not in the contralateral striatum. The magnitude of the attenuation in the ipsilateral striatum was directly proportional to the percent depletion of dopamine. Similarly degeneration of dopaminergic terminals produced by a unilateral application of 6-OHDA into the striatum lowered spontaneous MUA and completely antagonized the dexamphetamine-induced increase in MUA in the dopamine-depleted striatum. Although the spontaneous MUA in striata contralateral to a local 6-OHDA treatment was significantly reduced, the response to dexamphetamine was normal. Both striatal and nigral application of 6-OHDA produced dopamine depletion in the ipsilateral striatum and an increase in striatal dopamine levels on the contralateral side. Striatal application of 6-OHDA did not alter dopamine levels in either the olfactory tubercles, piriform cortex or cingulate cortex. It is concluded that the increase in MUA observed in the striatum following dexamphetamine treatment is critically dependent upon the release of dopamine in the striatum. These results support the concept that dopamine may have an excitatory action on some striatal neurons.
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D004594:Electrophysiology; D006892:Hydroxydopamines / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D016627:Oxidopamine; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects* / Q000502:physiology
D006892:Hydroxydopamines; D016627:Oxidopamine; D003913:Dextroamphetamine; D004298:Dopamine