Relapse of Paranoid Psychotic State in Methamphetamine Model of Schizophrenia

Abstract

The study of the clinical course of methamphetamine (MAP) psychosis yields insights into the biological aspect of the relapse of the paranoid psychotic state with hallucination in schizophrenia. A series of MAP psychosis studies in Japan conducted over a period of more than four decades revealed three types of clinical courses of MAP psychosis after discontinuation of MAP: transient type, prolonged type, and persistent type. Identification of the latter two indicates a lasting change in the brain that produces and maintains a schizophrenia-like paranoid psychotic state without MAP. The characteristic course seen in the transient type is acute recurrence of the psychotic state after a long remission period, almost identical to the initial episode, due to reuse of MAP or to psychological stressors. Such lasting vulnerability of the brain to schizophrenia-like psychotic symptoms may be caused by a lasting sensitization of the brain to the psychotogenic action of MAP resulting from its chronic abuse. Experimental studies using animals sensitized to MAP-induced stereotypy suggest that lasting enhancement of MAP-induced dopamine release in the striatum and nucleus accumbens is related to the development and expression of brain vulnerability to schizophrenic symptoms.

Association study between brain‐derived neurotrophic factor gene polymorphisms and methamphetamine abusers in Japan

“…Cocaine and heroine were rarely abused in the present study. Prognosis of MAP psychosis was various among patients, and some patients showed continuous psychotic symptoms even after MAP discontinuance as previously reported (Sato et al, 1992;Ujike, 2002). Therefore, patients were divided into two categories of prognosis, transient-type and prolonged-type, based on duration of psychotic state after MAP discontinuance.…”

“…Use of MAP induces a strong psychological dependence, and repeated usage frequently results in psychotic states, which symptoms are similar to those of paranoid-type schizophrenia (Sato et al, 1992;Ujike, 2002). It has been demonstrated that BDNF plays a role in the survival and differentiation of midbrain dopaminergic neurons in vivo (Hyman et al, 1991) and in vitro (Spina et al, 1992), and that chronic BDNF treatment enhances locomotor activity and conditioned reward to cocaine (Horger et al, 1999).…”

Homers regulate drug-induced neuroplasticity: Implications for addiction

“…Like other amphetamines, methamphetamine increases extracellular levels of monoamines by disrupting vesicular storage and reversing the plasma membrane transporter [262][263][264]. While methamphetamine's effects upon the monoaminergic systems have received considerable experimental attention [for reviews, [264][265][266][267][268][269][270], less is known regarding the regulation of corticoaccumbens glutamate and glutamate receptor expression by amphetamine and methylated analogs. Acute administration of amphetamines is reported to produce either no change or a delayed rise in extracellular glutamate levels within striatal regions [59][60][61][62]271,272], while an acute injection of methamphetamine, but not amphetamine, elevates PFC glutamate levels [271].…”

Increased methamphetamine‐induced locomotor activity and behavioral sensitization in histamine‐deficient mice

“…Methamphetamine (METH) is a central nervous system stimulant that can be injected, smoked, snorted or ingested orally; its prolonged use results in dependence and psychosis which is actually indistinguishable from the paranoid type schizophrenia (Snyder 1973;Sato et al 1992;Pierce and Kalivas 1997). In laboratory animals, METH induces increase of locomotor activity and stereotyped behavior, by inhibiting the reuptake and facilitating the release of dopamine (DA), and repeated administration of METH causes a progressive and long-lasting augmentation of locomotion and stereotyped behavior, which is called behavioral sensitization, one of the animal models of METH dependence and psychosis (Seiden et al 1993;Segal and Kuczenski 1994;Giros et al 1996;Jones et al 1998).…”