Amphetamine Withdrawal: Depression and M.H.P.G. Excretion

Schildkraut, J J; Watson, Robert; Draskoczy, PaulR.; Hartmann, Ernest

doi:10.1016/s0140-6736(71)92645-6

Cited by 55 publications

(15 citation statements)

References 10 publications

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“…3a), suggesting the expression of anxiety-related behavior. As expected on the basis of human observations [26,27], it is likely that decreased norepinephrinergic tone induces a dysphoric state during AMPH withdrawal including anxiety. Therefore, mice treated with a fixed-dose of METH are a good animal model of anxiety-related behavior in AMPH withdrawal in humans.…”

Section: Discussionsupporting

confidence: 58%

“…Similarly, the expression of anxiety during AMPH withdrawal [1,2] may be attributed to changes in NE neurotransmission in the cerebral cortex during the postdrug period. This possibility is supported by evidence that the urinary excretion of MHPG decreased after AMPH withdrawal in humans [26,27] because urinary MHPG excretion serves as an index of brain NE synthesis and metabolism [30,31]. The expression of anxiety-related behavior in parallel with decreases in the cerebral level of MHPG and NE turnover is an important finding in mice after the administration of a fixed dose of METH, since there is little evidence available regarding the association between neurochemistry and the behavioral aspects of anxiety during AMPH withdrawal in mice [13].…”

Section: Discussionmentioning

confidence: 78%

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Withdrawal from Fixed-Dose Injection of Methamphetamine Decreases Cerebral Levels of 3-Methoxy-4-hydroxyphenylglycol and Induces the Expression of Anxiety-Related Behavior in Mice

Kitanaka

Tatsuta

et al. 2010

Neurochem Res

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A variety of drug treatment regimens have been proposed to model the dysphoric state observed during methamphetamine (METH) withdrawal in rats, but little has been established in experiments using mice. In male ICR mice, a fixed-dose injection regimen of METH (1.0 or 2.5 mg/kg, i.p., twice daily for 10 consecutive days) induced a significant decrease in the time spent in open arms in an elevated plus maze after 5 days of drug abstinence. Under an escalating-dose injection regimen (0.2-2.0 mg/kg, i.p., 3 times daily for 4 days, total: 15 mg/kg/animal) or continuous subcutaneous administration with osmotic mini-pumps (15 or 76 mg/kg of METH for 2 weeks), no significant behavioral change was observed after 5 days of drug abstinence, compared with control animals. Reduced gains in body weight were observed during repeated treatment with METH in the fixed-dose injection and mini-pump treatment regimens, but not the escalating-dose injection regimen. HPLC analysis revealed significant decreases in the level of cerebral 3-methoxy-4-hydroxyphenylglycol, a norepinephrine metabolite, and norepinephrine turnover, which may be attributed to the expression of anxiety-related behavior in the elevated plus maze. These observations suggest that the mice treated with a fixed-dose of METH may model the anxiety-related behavior observed in the dysphoric state induced by METH withdrawal in humans.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 78%

Withdrawal from Fixed-Dose Injection of Methamphetamine Decreases Cerebral Levels of 3-Methoxy-4-hydroxyphenylglycol and Induces the Expression of Anxiety-Related Behavior in Mice

Kitanaka

Tatsuta

et al. 2010

Neurochem Res

View full text Add to dashboard Cite

show abstract

“…There is a possibility that decreased norepinephrinergic tone may induce the dysphoric state of AMPH withdrawal. This possibility is supported by evidence that the urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) decreased after AMPH withdrawal in humans [24,98]. Urinary MHPG excretion serves as an index of brain norepinephrine synthesis and metabolism [99,100].…”

Section: Postmortem Brain Tissue Levels Of Dopamine and Metabolites Amentioning

confidence: 99%

Neurochemical Consequences of Dysphoric State During Amphetamine Withdrawal in Animal Models: A Review

Kitanaka

Takemura

2007

Neurochem Res

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Chronic abuse of amphetamines, such as d-amphetamine (AMPH) and d-methamphetamine, results in psychological dependence, a condition in which the drug produces a feeling of satisfaction and a drive that requires periodic or continuous administration of the drug to produce overwhelming pleasure or to avoid discomfort such as dysphoria. The dysphoric state of AMPH withdrawal has been recognized as depressive syndromes, such as anhedonia, depression, anxiety, and social inhibition, in early drug abstinence. Medication for treatment of the dysphoric state is important for AMPH abusers to avoid impulsive self-injurious behavior or acts that are committed with unconscious or uncontrolled suicidal ideation. However, successful treatments for AMPH withdrawal remain elusive, since the exact molecular basis of the expression of dysphoria has not been fully elucidated. This review focuses on the molecular aspects of AMPH withdrawal as indexed by neurochemical parameters under a variety of injection regimens (for example, levels of brain monoamines and their metabolites, and gamma-aminobutyric acid, expression of genes and proteins involved in neuronal activity, and monoamine metabolism and availability) in rodent models which exhibit significant phenotypic features relevant to the syndromes of AMPH withdrawal in humans.

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“…1976], As shown in figure 2. the same phenomenon applies to opiates, whereas it is known that amphetamine with drawal is accompanied by signs of adrenergic failure [Schildkraut et al, 1971], These data refer to the acute phase of withdrawal, but there is now evidence in animals of a delayed phase of withdrawal, which may last for several months. It may be speculated that in alcoholics and opiate addicts, tricyclics worsen the withdrawal symptomatology because of their aminergic properties; this phenomenon would mask their antidepressant effect.…”

Section: Potential Medical Use Of Trazodonementioning

confidence: 98%

Trazodone and the Mental Pain Hypothesis of Depression

Silvestrini¹

1986

Neuropsychobiology

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The mental pain hypothesis used to develop trazodone is illustrated, together with its medical and methodological implications. Trazodone possesses a well documented antidepressant activity, which indirectly confirms the above hypothesis. It lacks the aminergic effects of other antidepressants and has a marked adrenolytic activity. Therefore it is potentially indicated in depressive states with adrenergic hyperactivation, such as during alcohol withdrawal. The methodological aspects of the approach taken for trazodone are also discussed, in the context of the strategies of psychopharmacological research.

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Amphetamine Withdrawal: Depression and M.H.P.G. Excretion

Cited by 55 publications

References 10 publications

Withdrawal from Fixed-Dose Injection of Methamphetamine Decreases Cerebral Levels of 3-Methoxy-4-hydroxyphenylglycol and Induces the Expression of Anxiety-Related Behavior in Mice

Withdrawal from Fixed-Dose Injection of Methamphetamine Decreases Cerebral Levels of 3-Methoxy-4-hydroxyphenylglycol and Induces the Expression of Anxiety-Related Behavior in Mice

Neurochemical Consequences of Dysphoric State During Amphetamine Withdrawal in Animal Models: A Review

Trazodone and the Mental Pain Hypothesis of Depression

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