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Absence of methamphetamine-induced conditioned place preference in weaver mutant mice.

ABSTRACT: Aims: G protein-activated inwardly rectifying potassium (GIRK) channels are related to rewarding effects of addictive drugs. The GIRK2 subunit is thought to play key roles in the reward system. Weaver mutant mice exhibit abnormal GIRK2 function and different behaviors that are caused by several addictive substances compared with wild-type mice. However, mechanisms of reward-related alterations in weaver mutant mice remain unclear. The present study investigated changes in the rewarding effects of methamphetamine (METH) in weaver mutant mice.

Methods: The rewarding effects of METH (4.0 mg/kg) were investigated using the conditioned place preference (CPP) paradigm. Extracellular dopamine level in the nucleus accumbens (NAc) was measured by in vivo microdialysis. To identify brain regions that were associated with these changes in rewarding effects, METH-induced alterations of Fos expression were investigated by immunohistochemical analysis.

Results: Weaver mutant mice exhibited a significant decrease in METH-induced CPP and dopamine release in the NAc. Methamphetamine significantly increased Fos expression in the posterior NAc (pNAc) shell in wild-type but not in weaver mutant mice.

Conclusions: Methamphetamine did not induce rewarding effects in weaver mutant mice. The pNAc shell exhibited a significant difference in neuronal activity between wild-type and weaver mutant mice. The present results suggest that the absence of METH-induced CPP in weaver mutant mice is probably related to an innate reduction of dopamine and decreased neural activity in the pNAc shell that is partially attributable to the change of GIRK channel function. GIRK channels, especially those containing the GIRK2 subunit, appear to be involved in METH dependence.

SUBMITTER: Ikekubo Y

PROVIDER: S-EPMC7722684 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Absence of methamphetamine-induced conditioned place preference in weaver mutant mice.

Ikekubo Yuiko Y Ide Soichiro S Hagino Yoko Y Ikeda Kazutaka K

Neuropsychopharmacology reports 20200819 4

<h4>Aims</h4>G protein-activated inwardly rectifying potassium (GIRK) channels are related to rewarding effects of addictive drugs. The GIRK2 subunit is thought to play key roles in the reward system. Weaver mutant mice exhibit abnormal GIRK2 function and different behaviors that are caused by several addictive substances compared with wild-type mice. However, mechanisms of reward-related alterations in weaver mutant mice remain unclear. The present study investigated changes in the rewarding ef ...[more]

PMID: 32812711

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Project description:Methamphetamine (METH) withdrawal anxiety symptom and relapse have been significant challenges for clinical practice, however, the underlying neuronal basis remains unclear. Our recent research has identified a specific subpopulation of choline acetyltransferase (ChAT+) neurons localized in the external lateral portion of parabrachial nucleus (eLPBChAT), which modulates METH primed-reinstatement of conditioned place preference (CPP). Here, the anatomical structures and functional roles of eLPBChAT projections in METH withdrawal anxiety and primed reinstatement were further explored. Methods: In the present study, a multifaceted approach was employed to dissect the LPBChAT+ projections in male mice, including anterograde and retrograde tracing, acetylcholine (Ach) indicator combined with fiber photometry recording, photogenetic and chemogenetic regulation, as well as electrophysiological recording. METH withdrawal anxiety-like behaviors and METH-primed reinstatement of conditioned place preference (CPP) were assessed in male mice. Results: We identified that eLPBChAT send projections to PKCδ-positive (PKCδ+) neurons in lateral portion of central nucleus of amygdala (lCeAPKCδ) and oval portion of bed nucleus of the stria terminalis (ovBNSTPKCδ), forming eLPBChAT-lCeAPKCδ and eLPBChAT-ovBNSTPKCδ pathways. At least in part, the eLPBChAT neurons positively innervate lCeAPKCδ neurons and ovBNSTPKCδ neurons through regulating synaptic elements of presynaptic Ach release and postsynaptic nicotinic acetylcholine receptors (nAChRs). METH withdrawal anxiety and METH-primed reinstatement of CPP respectively recruit eLPBChAT-lCeAPKCδ pathway and eLPBChAT-ovBNSTPKCδ pathway in male mice. Conclusion: Our findings put new insights into the complex neural networks, especially focusing on the eLPBChAT projections. The eLPBChAT is a critical node in the neural networks governing METH withdrawal anxiety and primed-reinstatement of CPP through its projections to the lCeAPKCδ and ovBNSTPKCδ, respectively.

Dataset Information

Absence of methamphetamine-induced conditioned place preference in weaver mutant mice.

Publications

Absence of methamphetamine-induced conditioned place preference in weaver mutant mice.

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