Supersensitivity of presynaptic receptors involved in the dopaminergic control of striatal high affinity glutamate uptake after 6-hydroxydopamine lesion of nigrostriatal dopaminergic neurons.
The effects on striatal high affinity glutamate uptake (HAGU) of an apomorphine injection administered either alone or along with an electrical stimulation of the frontal cortex were compared between intact control rats and animals with 6-hydroxydopamine (6-OHDA) induced lesions of the nigrostriatal dopaminergic neurons. 6-OHDA injury was previously shown to have no effect either on basal HAGU or on the HAGU increase occurring in response to cortical stimulation. Apomorphine injected 1 h before HAGU determination at a dose of 5 mg/kg did not modify basal HAGU but totally abolished HAGU responsiveness to cortical stimulation applied 30 min after the apomorphine administration in both groups of animals. However, the duration of apomorphine induced inhibition of the cortically evoked striatal HAGU response in animals with 6-OHDA injury greatly exceeded that observed in intact rats. Indeed, in intact animals, cortical stimulation again became able to increase striatal HAGU when applied more than 6 h after apomorphine injection, while in 6-OHDA injected rats, HAGU responsiveness to cortical stimulation was restored only as from 7 days after apomorphine administration. Moreover, in rats given 6-OHDA injections apomorphine efficiently inhibited the activating effect of cortical stimulation on HAGU at doses at least 20 times lower than those required to obtain the same effect in intact animals. These results suggest that in both intact and 6-OHDA injected rats, apomorphine acts by counteracting the HAGU increase occurring in response to cortical stimulation and that the sites involved in this action develop a supersensitivity response to striatal dopaminergic deafferentation.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006892:Hydroxydopamines; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D017448:Receptors, Dopamine D2; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*
D005971:Glutamates; D006892:Hydroxydopamines; D017448:Receptors, Dopamine D2; D011957:Receptors, Opioid; D018698:Glutamic Acid; D016627:Oxidopamine; D001058:Apomorphine; D004298:Dopamine