Stress sensitization induced by stressor and methamphetamine]

Repetitive or acute treatment of methamphetamine (MAP) or amphetamine (AMP) induces sensitization to both subsequent challenge treatment of the drugs, and exposure to emotional and physiological stress. In addition, chronic treatment of AMP enhanced DA utilization/release in striatum. Similarly, repetitive exposure to footshock or tail shock stress induces sensitization of noradrenaline or 3-methoxy-4-hydroxyphenylglycol (MHPG) to subsequent mild stress and to small amounts of AMP or MAP injection. Striatum, nucleus accumbens and prefrontal dopaminergic systems have an important role in the development of this sensitization. Immediate early gene (IEG) expression in the hypothalamus, nucleus accumbens and striatum may be involved in this process. Neurobiological vulnerability to schizophrenia may be induced by the interaction of multiple gene disposition and environmental insult, and schizophrenia onset and/or relapse in response to mild, non-specific stress. Stress-sensitive systems therefore are postulated in the pathophysiology of schizophrenia. In this regard, mesolimbic DA systems may be involved in the pathophysiology of schizophrenia. In contrast to MAP- or AMP- and stress-induced sensitization, haloperidol and clozapine induce IEG expression in the caudate-putamen and amygdala. Collectively, MAP- or AMP-induced sensitization may, in part, share an early functional process of neurobiological mechanisms.