The Role of Noradrenergic and Dopaminergic Hyperactivity in the Development of Spontaneous Recurrence of Methamphetamine Psychosis and Susceptibility to Episode Recurrence

Abstract

The role of dopaminergic activity in susceptibility of methamphetamine (MAP) psychosis (flashbacks) to subsequent spontaneous recurrences was studied. Plasma monoamine metabolite levels were assayed in 23 flashbackers, of whom 10 experienced a single flashback, 8 exhibited subsequent flashbacks and 5 with the last episode; 18 nonflashbackers with a history of MAP psychosis; 9 subjects with persistent MAP psychosis; and 19 MAP user and 10 nonuser controls. All flashbackers had undergone frightening stressful experiences during previous MAP use. Their flashbacks were triggered by mild psychosocial stressors. Plasma norepinephrine (NE) levels increased with the increase in plasma levels of 3-methoxytyramine (3-MT), an index of dopamine release, during flashbacks in the 23 flashbackers. Of these, the 8 with subsequent episodes had markedly increased NE levels and increased 3-methoxytyramine levels during flashbacks. However, the 5 flashbackers with the last episode had moderately increased NE levels, and the 10 with a single episode displayed small increases in NE levels during flashbacks. Their 3-MT levels did not significantly differ from the levels in the control groups. Thus, increased DA release in addition to robust noradrenergic hyperactivity in response to mild psychosocial stressors may be important in susceptibility to subsequent flashbacks.

Stress-Induced Dopamine Release in Humans at Risk of Psychosis: a [11C]Raclopride PET Study

“…Third, although our particular interest is in schizophrenia vulnerability, our personality measures of vulnerability are sensitive to risk for psychosis, including affective psychosis (Erlenmeyer-Kimling et al, 1993;Chapman et al, 1994). Increased DA release in response to stress may represent a risk factor for psychosis in general, rather than a risk factor for schizophrenia per se (Yui et al, 2004). Fourth, we did not find DA release to be correlated with cortisol levels, as was found in our previous study (Pruessner et al, 2004), nor did we observe differences in cortisol between groups, a result likely due to our low number of participants.…”

The Effects of Locus Coeruleus and Norepinephrine in Methamphetamine Toxicity

“…In fact a variety of neurotransmitters are released under METH administration - namely, serotonin [66] glutamate [67-69] and acetylcholine [70, 71]. Among these, catecholamine neurons are considered as the main target since METH is a powerful DA and NE releaser [72, 73]. As a consequence, repetitive administration of METH leads to DA-and NE-dependent behavioural sensitization, which can be reproduced in different species.…”

“…Accordingly, when evaluating the behavioural effects induced by a selective NET blocker in animals, this may reproduce the effects of amphetamines [116]. Lending further implications to these findings, some works have emphasized the role of increased NE release in producing sensitization following METH administration [73]. …”

Effect of the environmental enrichment on the severity of psychological dependence and voluntary methamphetamine consumption in methamphetamine withdrawn rats

“…Recent findings have shown that chronic METH use alters synaptic plasticity in the brain, which may contribute to its adverse effects [35], include dependence, withdrawal syndrome and drug craving [9,17,34]. The METH use causes neurotoxicity in multiple neurotransmitter systems [13,18,41]. METH-induced alterations in dopamine levels in mesolimbic, nigrostriatal systems and prefrontal cortex involve in craving and rewarding effects of drug [16,28].…”