Effects Of Typical and Atypical Antischizophrenic Neuroleptics On Locomotor Activity and Monoamine Metabolism In Male Sprague Dawley Rats
Green, Jahmal Bashan
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Typical neuroleptics bind preferentially to D2 dopaminergic receptors, reducing symptoms of schizophrenia, but eliciting mild to severe side effects. The present study investigated the behavioral and biochemical effects of atypical neuroleptics and their ability to treat schizophrenia without the adverse effects seen in classical neuroleptics using different dopaminergic binding receptors. Clozapine, Remoxipride, (atypical neuroleptics) and PD128907, a D3 dopaminergic agonist, were tested in the male Sprague Dawley Rat. Observations of dopamine synthesis and metabolite production (dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)) were made within the cerebral cortex to measure dopaminergic activity. The results of atypical compounds were then compared to those of haloperidol, the most common classical neuroleptic. The current study revealed pronounced behavioral differences between haloperidol and the atypical neuroleptics, with atypical drugs exhibiting no catalepsy and minimal extrapyramidal side effects compared to haloperidol. Biochemically, atypical neuroleptics exhibited a more stable profile in terms of dopamine synthesis, release, and metabolite production compared with haloperidol results. It was also observed in this study that stimulation of the dopamine D3 postsynaptic receptors exhibited psychomotor inhibitory and activation responses within the rat model with varying concentrations. These results suggest the possibility of alleviating schizophrenic symptoms through the stimulation of the D3 receptor, which may function in dopamine regulation within the brain.