Effect of glutamate receptor antagonists on excitatory postsynaptic potentials in striatum.

Glutamate, as the main transmitter of corticostriatal pathway, has a crucial role in the regulation of the activity of striatal cells as well as in pathogenesis of some diseases characterized by striatal malfunction caused by overexcitation of neurons. In the present study, the role of ionotropic excitatory amino acid receptors was investigated in the striatal synaptic transmission. Using conventional intracellular electrophysiological methods in brain slices, we have investigated the effects of the N-methyl-D-aspartate (NMDA) antagonist (+/-) 2-amino-5-phosphono-valerate (APV) and the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) antagonist (+/-) 1-(4-aminophenyl)-3-methyl-carbamoyl-7,8-methylenedioxy-5H-2,3-benzodiaz epine (GYKI 53655) on the excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of corpus callosalpham. The AMPA antagonist significantly decreased electrically evoked responses and a weak inhibition was also observed after APV application. The results were compared to similar data obtained in a cortical slice study.

The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders.

OBJECTIVE: --The A1 allele of the Taq I polymorphism of the dopamine D2 receptor (DRD2) gene has been earlier reported to occur in 69% of alcoholics, compared with 20% of controls. Other research has reported no significant difference in the prevalence of the A1 allele in alcoholics vs controls and no evidence that the DRD2 gene was linked to alcoholism. We hypothesized that these seemingly conflicting results might be because increases in the prevalence of the A1 allele may not be specific to alcoholism. Thus, we examined other disorders frequently associated with alcoholism or those believed to involve defects in dopaminergic neurotransmission. DESIGN: --Case comparison study. To minimize the effect of racial differences in gene frequencies, the study was restricted to non-Hispanic whites. SETTING: --Ambulatory and hospitalized patients. RESULTS: --Among all known controls (n = 314), 77 (24.5%) carried the A1 allele. Of the 69 controls known not to be alcoholics, 10 (14.5%) carried the A1 allele. The prevalence of the A1 allele was significantly increased in patients with Tourette's syndrome (44.9%, n = 147), attention deficit hyperactivity disorder (46.2%, n = 104), autism (54.5%, n = 33), alcoholism (42.3%, n = 104), and posttraumatic stress disorder (45.7%, n = 35). After correction for multiple comparisons (requiring P less than .0009 for significance), all remained significant except posttraumatic stress disorder. The prevalence of the A1 allele was not significantly increased in patients with depression, panic attacks, Parkinson's disease, or obesity. The prevalence of the A1 allele in drug addiction and schizophrenia was only significant when compared with that of controls who were not alcoholics, and no correction was made for multiple comparisons. CONCLUSION: --These results suggest the A1 allele of the DRD2 gene is associated with a number of behavior disorders in which it may act as a modifying gene rather than as the primary etiological agent.