Chronic neuroleptic treatment: D2 dopamine receptor supersensitivity and striatal glutamatergic transmission.
We studied the in vitro electrical activity of rat neostriatal neurons following chronic neuroleptic treatment. In haloperidol-treated rats, unlike naive animals, activation of neostriatal D2 dopamine receptors induced a potent presynaptic inhibition of glutamate-mediated excitatory synaptic potentials. Haloperidol treatment did not affect the intrinsic membrane properties of the neostriatal neurons. Pre- and postsynaptic physiological responses to direct and indirect gamma-aminobutyric acid (GABA)-ergic and cholinergic agonists were not affected by chronic haloperidol treatment. These findings suggest that movement disorders induced by chronic neuroleptic treatment may result, at least in part, from a hypersensitivity of presynaptic D2 dopamine receptors regulating the release of glutamate.
Clinica Neurologica, Dip. Sanità, II Università degli Studi di Roma, Italy.
P
P
Calabresi
M
M
De Murtas
N B
NB
Mercuri
G
G
Bernardi
D000375:Aging / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D003342:Corpus Striatum / Q000378:metabolism*; D004873:Ergolines / Q000494:pharmacology; D005973:Glutamine / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D014150:Antipsychotic Agents; D004873:Ergolines; D010277:Parasympathomimetics; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D005973:Glutamine; D019257:Quinpirole; D006220:Haloperidol