Cortical modulation of striatal function.
The effect of bilateral section of the corticostriatal projections or of selective bilateral ablation of the frontal cortex on behavioral and biochemical parameters related to striatal function were investigated in the rat. Either lesion almost completely prevented the cataleptogenic action of haloperidol: this effect was observed as soon as 3 days and lasted for at least 3 months after surgery, paralleling a reduction in striatal glutamate uptake. Also, such lesions enhanced the apomorphine-induced stereotyped behavior (as measured 21 days after surgery). In the striatum, dopamine, dihydroxyphenylacetic acid, acetylcholine and substance P levels as well as choline acetyltransferase and glutamic acid decarboxylase activities were unaffected 10 or 21 days after either type of lesion. In the substantia nigra, substance P levels were unchanged 10 days following suction of the frontal cortex, but glutamic acid decarboxylase was reduced at 21 days postsurgery. Cortical lesions only partially prevented the reduction in striatal acetylcholine concentrations and did not affect the increase in striatal dihydroxyphenylacetic acid caused by haloperidol. Finally, lesions of the corticostriatal pathways failed to affect the apomorphine-induced increase in striatal acetylcholine levels, reduction of the potassium (20 mM) evoked [3H]acetylcholine release in striatal slices preloaded with [3H]choline and decrease of striatal dihydroxyphenylacetic acid concentrations. These findings indicate that the frontal cortex influences extrapyramidal function by a mechanism which--in behavioral terms--is antagonistic to dopamine-mediated events. As indicated by the biochemical data, this mechanism does not involve changes in striatal dopaminergic and cholinergic neuron activity. This mechanism may utilize: (1) corticostriatal glutamatergic neurons as suggested by the reduction in striatal glutamate uptake following lesions; and (2) GABAergic pathways as suggested by the reduction of nigral glutamic acid decarboxylase activity as well as by the finding that GABA receptor agonists reinstate haloperidol-induced catalepsy.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D005116:Extrapyramidal Tracts / Q000502:physiology; D005625:Frontal Lobe / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000502:physiology; D013373:Substance P / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D015102:3,4-Dihydroxyphenylacetic Acid; D013373:Substance P; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D006220:Haloperidol; D000109:Acetylcholine; D004298:Dopamine