In this study, we examined the relationship between increased sensitivity to stress
associated with noradrenergic hyperactivity and dopaminergic changes, and susceptibility
to subsequent spontaneous recurrences of methamphetamine (MAP) psychosis (i.e., flashbacks).
The subjects were 81 physically healthy females. Plasma monoamine metabolite
levels were assayed in: 19 flashbackers, of whom 11 experienced a single flashback
and 8 exhibited subsequent flashbacks; 20 non-flashbackers with a history of MAP psychosis;
8 subjects with persistent MAP psychosis; and 23 MAP users and 11 non-user controls.
All 19 flashbackers had undergone frightening and stressful experiences during previous
MAP use. Mild psychosocial stressors then triggered their flashbacks. During flashbacks,
plasma norepinephrine levels increased, with a small increase in plasma levels of
3-methoxytyramine, which is an index of dopamine release. Among the 19 flashbackers,
the 8 with subsequent episodes had increased NE levels and slightly increased 3-methoxytyramine
levels, while the 11 with a single episode displayed small increases in norepinephrine
and 3-methoxytyramine levels. Thus, noradrenergic hyperactivity and increased dopamine
release in response to mild psychosocial stressors may be responsible for the development
of flashbacks. Robust noradrenergic hyperactivity with slightly increased DA release
in response to mild stress may induce susceptibility to subsequent flashbacks. Flashbacks
and schizophrenia may share the pathophysiology of susceptibility to recurrence of
paranoid-hallucinatory states such as stress sensitization, and also noradrenergic
hyperactivity and enhanced DA release. Thus, flashbacks may provide an appropriate
model of susceptibility to paranoid-hallucinatory states of schizophrenia. The model
psychosis is a potential tool for validating basic neurobiological concepts thought
to be related to the schizophrenia. A better understanding of the neurobiological
mechanisms of susceptibility to recurrence could provide useful information in the
development of strategies for preventing relapse.
References
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Psychostimulant-induced behavioral effects: possible models of schizophrenia. In: Lipton MA, DiMascio A, Killam KF: Psychopharmacology: a generation of progress. Rave
Press, New York 1978: 1113-1123
nibrin@jichi.ac.jp
