Oral movements induced by interference with nigral GABA neurotransmission: relationship to tardive dyskinesias.
Previous studies have shown that the emergence of spontaneous dyskinetic behaviors, such as vacuous chewing movements, following several months of neuroleptic treatment in the rat, is correlated with depletion of nigral GABA. To explore the specificity of this relationship, we acutely interfered with nigral GABA transmission pharmacologically, by microinfusing either the GABA receptor antagonist, bicuculline, or the GABA-depleting agent, isoniazid, bilaterally into substantia nigra. We found that both acute treatments induced vacuous chewing movements in rats. Moreover, the time to onset of action of each of these drugs corresponded to the onsets of their respective effects on GABA transmission. In addition, we found that the application of muscimol into the target field of the nigrotegmental projection, which has been shown to block gnawing elicited by nigral GABA receptor stimulation, completely abolished elicitation of vacuous chewing movements by intranigral isoniazid. In contrast, bilateral microinfusions of muscimol into the nigrocollicular target region, in the deep layers of superior colliculus, blocked elicitation of gnawing by intranigral muscimol, but completely spared elicitation of vacuous chewing movements by intranigral isoniazid. We conclude that qualitatively different dyskinetic syndromes can be produced by bidirectional perturbations of nigral GABA function and are differentially mediated by nigrotegmental and nigrotectal projections. These syndromes may represent animal models of distinct components of extrapyramidal side effects of chronic neuroleptic administration.
Gunne
L M
LM
Psychiatric Research Center, Uppsala, Sweden.
Bachus
S E
SE
Gale
K
K
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D018756:GABA Antagonists; D007267:Injections; D007538:Isoniazid / Q000494:pharmacology; D008409:Mastication; D009055:Mouth / Q000502:physiology*; D009068:Movement; D009118:Muscimol / Q000494:pharmacology; D013378:Substantia Nigra / Q000502:physiology*; D009435:Synaptic Transmission; D003336:Tectum Mesencephali; D013681:Tegmentum Mesencephali; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018756:GABA Antagonists; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D007538:Isoniazid; D001640:Bicuculline