The Effect of the Impulsivity on the Conditioned Placed Preference and Behavioral Sensitization Induced by Morphine in Rats

Abstract Background Methamphetamine (METH) is one of the most widely abused illicit substances worldwide; unfortunately, its addiction mechanism remains unclear. Based on accumulating evidence, changes in gene expression and chromatin modifications might be related to the persistent effects of METH on the brain. In the present study, we took advantage of METH-induced behavioral sensitization as an animal model that reflects some aspects of drug addiction and examined the changes in gene expression and histone acetylation in the prefrontal cortex (PFC) of adult rats. Methods We conducted mRNA microarray and chromatin immunoprecipitation (ChIP) coupled to DNA microarray (ChIP-chip) analyses to screen and identify changes in transcript levels and histone acetylation patterns. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were performed to analyze the differentially expressed genes. We then further identified alterations in ANP32A (acidic leucine-rich nuclear phosphoprotein-32A) and POU3F2 (POU domain, class 3, transcription factor 2) using qPCR and ChIP-PCR assays. Results In the rat model of METH-induced behavioral sensitization, METH challenge caused 275 differentially expressed genes and a number of hyperacetylated genes (821 genes with H3 acetylation and 10 genes with H4 acetylation). Based on mRNA microarray and GO and KEGG enrichment analyses, 24 genes may be involved in METH-induced behavioral sensitization, and 7 genes were confirmed using qPCR. We further examined the alterations in the levels of the ANP32A and POU3F2 transcripts and histone acetylation at different periods of METH-induced behavioral sensitization. H4 hyperacetylation contributed to the increased levels of ANP32A mRNA and H3/H4 hyperacetylation contributed to the increased levels of POU3F2 mRNA induced by METH challenge-induced behavioral sensitization, but not by acute METH exposure. Conclusions The present results revealed alterations in transcription and histone acetylation in the rat PFC by METH exposure and provided evidence that modifications of histone acetylation contributed to the alterations in gene expression caused by METH-induced behavioral sensitization.

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MK-801 prevents the development of behavioral sensitization during repeated morphine administration

Synapse ◽

10.1002/syn.890160207 ◽

1994 ◽

Vol 16 (2) ◽

pp. 137-147 ◽

Cited By ~ 92

Author(s):

Michael Jeziorski ◽

Francis J. White ◽

Marina E. Wolf

Keyword(s):

Behavioral Sensitization ◽

Mk 801 ◽

Morphine Administration

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Lithium Pharmacology and a Potential Role of Lithium on Methamphetamine Abuse and Dependence

Current Drug Research Reviews ◽

10.2174/2589977511666190620141824 ◽

2019 ◽

Vol 11 (2) ◽

pp. 85-91 ◽

Cited By ~ 2

Author(s):

Nobue Kitanaka ◽

Frank Scott Hall ◽

George Richard Uhl ◽

Junichi Kitanaka

Keyword(s):

Molecular Mechanisms ◽

Behavioral Sensitization ◽

Tryptophan Hydroxylase ◽

Glycogen Synthase ◽

Lithium Treatment ◽

Glycogen Synthase Kinase ◽

Therapeutic Effects ◽

Potential Candidate ◽

Glycogen Synthase Kinase 3Β ◽

Methamphetamine Abuse

Background:The effectiveness of lithium salts in neuropsychiatric disorders such as bipolar disorder, Alzheimer’s disease, and treatment-resistant depression has been documented in an extensive scientific literature. Lithium inhibits inositol monophosphatase, inositol polyphosphate 1- phosphatase, and glycogen synthase kinase-3 and decreases expression level of tryptophan hydroxylase 2, conceivably underlying the mood stabilizing effects of lithium, as well as procognitive and neuroprotective effects. However, the exact molecular mechanisms of action of lithium on mood stabilizing and pro-cognitive effects in humans are still largely unknown.Objective:On the basis of the known aspects of lithium pharmacology, this review will discuss the possible mechanisms underlying the therapeutic effects of lithium on positive symptoms of methamphetamine abuse and dependence.Conclusion:It is possible that lithium treatment reduces the amount of newly synthesized phosphatidylinositol, potentially preventing or reversing neuroadaptations contributing to behavioral sensitization induced by methamphetamine. In addition, it is suggested that exposure to repeated doses of methamphetamine induces hyperactivation of glycogen synthase kinase-3β in the nucleus accumbens and in dorsal hippocampus, resulting in a long-term alterations in synaptic plasticity underlying behavioral sensitization as well as other behavioral deficits in memory-related behavior. Therefore it is clear that glycogen synthase kinase-3β inhibitors can be considered as a potential candidate for the treatment of methamphetamine abuse and dependence.

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