Chapter 12 Neuroleptics and striatal neuropeptide gene expression

Abstract

Neuroleptics (nerve seizing) are a broad spectrum of agents that historically, were introduced into clinical medicine due to their ability to potentiate the effects of anaesthetics. Administered alone, these compounds result in a diminished state of arousal and a tendency to sleep without loss of consciousness.Thus, it was not long before the beneficial “soothing” ability of these compounds was recognized by clinical psychiatrists in the treatment of psychosis. Whilst treatment of psychotic patients with neuroleptics may not necessarily be an effective “cure,” they may be effective in controlling/suppressing the socially unacceptable behavior patterns exhibited by these patients. Consequently, chlorpromazine, the archetypal neuroleptic, was introduced into clinical psychiatry in the 1950s as an effective treatment for psychosis. Subsequent biochemical studies in the experimental animals demonstrated that the sedated behavior induced by these compounds could be mimicked by drugs that blocked dopamine (DA) neurotransmission, for example, these agents could inhibit stereotypic behavior induced by amphetamine, a non-selective DA agonist, or as in the case of reserpine, isolated from Rauwolfiaserpentina, and used in the 1930s in the treatment of insanity and hypertension, deplete catecholamine stores rendering experimental subjects rigid and bradykinetic. Consequently, interest in the physiology and neurobiology of catecholamines and the diversity of their roles in mediating cognition and locomotion has exploded over the past three decades and progressed rapidly. Neuroleptics, DA receptor antagonists, are now widely used in clinical medicine, for treating both psychiatric and neurodegenerative disorders, where a dysfunction in DA transmission has been implicated; haloperidol (a typical neuroleptic) is used in the treatment of Gilles de la Tourette's Syndrome, clozapine (an atypical neuroleptic) is used in the treatment of schizophrenia, while L-Dopa (DA precursor) is used successfully in the treatment of Parkinson's disease.