Effects Of Typical and Atypical Antischizophrenic Neuroleptics On Locomotor Activity and Monoamine Metabolism In Male Sprague Dawley Rats
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Authors
Green, Jahmal Bashan
Issue Date
1995
Type
Thesis
Language
en_US
Keywords
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Abstract
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.
Description
v, 48 p.
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