An Amphetamine Model of Manic Depressive Illness

Mamelak, Mortimer

doi:10.1159/000468341

Cited by 31 publications

(17 citation statements)

References 49 publications

(88 reference statements)

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“…This hyperlocomotion behavior induced by drugs, such as amphetamine, in rodents is a widely used animal model for the manic phase of bipolar disorder and is especially useful for testing the efficacy of antimanic drugs (Einat et al, 2003b; Gould and Einat, 2007). Clinically, there is evidence that dopamine agonist drugs can increase the susceptibility to mania in bipolar disorder patients and the effects of dopamine agonists, such as methylphenidate, can be lessened with concurrent use of lithium (Mamelak, 1978; Huey et al, 1981; van Kammen et al, 1985; Carlson et al, 1992). …”

Section: Lithium and Gsk-3mentioning

confidence: 99%

Molecular actions and clinical pharmacogenetics of lithium therapy

Can

Schulze

Gould

2014

Pharmacology Biochemistry and Behavior

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Mood disorders, including bipolar disorder and depression, are relatively common human diseases for which pharmacological treatment options are often not optimal. Among existing pharmacological agents and mood stabilizers used for the treatment of mood disorders, lithium has a unique clinical profile. Lithium has efficacy in the treatment of bipolar disorder generally, and in particular mania, while also being useful in the adjunct treatment of refractory depression. In addition to antimanic and adjunct antidepressant efficacy, lithium is also proven effective in the reduction of suicide and suicidal behaviors. However, only a subset of patients manifests beneficial responses to lithium therapy and the underlying genetic factors of response are not exactly known. Here we discuss preclinical research suggesting mechanisms likely to underlie lithium’s therapeutic actions including direct targets inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) among others, as well as indirect actions including modulation of neurotrophic and neurotransmitter systems and circadian function. We follow with a discussion of current knowledge related to the pharmacogenetic underpinnings of effective lithium therapy in patients within this context. Progress in elucidation of genetic factors that may be involved in human response to lithium pharmacology has been slow, and there is still limited conclusive evidence for the role of a particular genetic factor. However, the development of new approaches such as genome-wide association studies (GWAS), and increased use of genetic testing and improved identification of mood disorder patients sub-groups will lead to improved elucidation of relevant genetic factors in the future.

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Section: Lithium and Gsk-3mentioning

confidence: 99%

Molecular actions and clinical pharmacogenetics of lithium therapy

Can

Schulze

Gould

2014

Pharmacology Biochemistry and Behavior

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“…As aforementioned, METH psychosis has been viewed as a pharmacological model of schizophrenia [Bell, 1965;Snyder, 1973]; however METH use has also been posited as a pharmacological model of mania [Mamelak, 1978;Jacobs and Silverstone, 1986] and during the withdrawal period a model for depression [Seltzer and Tonge, 1975;Kitanaka et al, 2008]. Thus, studies examining the genetic architecture of METH use disorders may also provide links to understanding the genetic complexities of a variety of other psychiatric disorders.…”

Section: Future Directionsmentioning

confidence: 99%

Genetic association studies of methamphetamine use disorders: A systematic review and synthesis

Bousman

Glatt

Everall

et al. 2009

American J of Med Genetics Pt B

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Efforts to understand the biological processes that increase susceptibility to methamphetamine (METH) use disorders (i.e., abuse, dependence, and psychosis) have uncovered several putative genotypic variants. However, to date a synthesis of this information has not been conducted. Thus, systematic searches of the current literature were undertaken for genetic-association studies of METH use disorders. Each gene's chromosomal location, function, and examined polymorphic markers were extracted. Frequencies, odds ratios and 95% confidence intervals for risk alleles, as well as sample size and power, were calculated. We uncovered 38 studies examining 39 genes, of which 18 were found to have a significant genotypic, allelic, and/or haplotypic association with METH use disorders. Three genes (COMT, DRD4, and GABRA1) were associated with METH abuse, nine (ARRB2, BDNF, CYP2D6, GLYT1, GSTM1, GSTP1, PDYN, PICK1, and SLC22A3) with METH dependence, two (AKT1 and GABRG2) with METH abuse/dependence, and four (DTNBP1, OPRM1, SNCA, and SOD2) with METH psychosis. Limitations related to phenotypic classification, statistical power, and potential publication bias in the current literature were noted. Similar to other behavioral, psychiatric, and substance use disorders, the genetic epidemiology of METH use disorders is complex and likely polygenic. National and international collaborative efforts are needed to increase the availability of large population-based samples and improve upon the power to detect genetic associations of small magnitude. Further, replication of the findings reviewed here along with further development of more rigorous methodologies and reporting protocols will aid in delineating the complex genetic epidemiology of METH use disorders.

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“…Stimulants alone have been shown to precipitate mania or hypomania in bipolar patients (Murphy et al, 1971;Mamelak, 1978;Anand et al, 2000), which is one reason why the effect of lithium on amphetamine models of mania might be of interest. In a double-blind study of depressed patients, the euphoriant and/or activating effects of amphetamine were also either attenuated or blocked by lithium (Van Kammen and Murphy, 1975).…”

Section: Lithium and Stimulants In Humansmentioning

confidence: 99%

The behavioral actions of lithium in rodent models: Leads to develop novel therapeutics

O’Donnell

Gould

2007

Neuroscience & Biobehavioral Reviews

121

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For nearly as long as lithium has been in clinical use for the treatment of bipolar disorder, depression, and other conditions, investigators have attempted to characterize its effects on behaviors in rodents. Lithium consistently decreases exploratory activity, rearing, aggression, and amphetamine-induced hyperlocomotion; and it increases the sensitivity to pilocarpine-induced seizures, decreases immobility time in the forced swim test, and attenuates reserpine-induced hypolocomotion. Lithium also predictably induces conditioned taste aversion and alterations in circadian rhythms. The modulation of stereotypy, sensitization, and reward behavior are less consistent actions of the drug. These behavioral models may be relevant to human symptoms and to clinical endophenotypes. It is likely that the actions of lithium in a subset of these animal models are related to the therapeutic efficacy, as well the side effects, of the drug. We conclude with a brief discussion of various molecular mechanisms by which these lithium-sensitive behaviors may be mediated, and comment on the ways in which rat and mouse models can be used more effectively in the future to address persistent questions about the therapeutically relevant molecular actions of lithium.

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An Amphetamine Model of Manic Depressive Illness

Cited by 31 publications

References 49 publications

Molecular actions and clinical pharmacogenetics of lithium therapy

Molecular actions and clinical pharmacogenetics of lithium therapy

Genetic association studies of methamphetamine use disorders: A systematic review and synthesis

The behavioral actions of lithium in rodent models: Leads to develop novel therapeutics

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