These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Methamphetamine increases dopamine release in the nucleus accumbens through calcium-dependent processes.
    Author: Yorgason JT, Hedges DM, Obray JD, Jang EY, Bills KB, Woodbury M, Williams B, Parsons MJ, Andres MA, Steffensen SC.
    Journal: Psychopharmacology (Berl); 2020 May; 237(5):1317-1330. PubMed ID: 31965252.
    Abstract:
    RATIONALE: Methamphetamine (METH) enhances exocytotic dopamine (DA) signals and induces DA transporter (DAT)-mediated efflux in brain striatal regions such as the nucleus accumbens (NAc). Blocking sigma receptors prevents METH-induced DA increases. Sigma receptor activation induces Ca2+ release from intracellular stores, which may be responsible for METH-induced DA increases. OBJECTIVES: The role of intracellular and extracellular Ca2+ in METH-induced DA increases and associated behavior was tested. METHODS: METH-induced Ca2+ release was measured in hNPC-derived DA cells using ratiometric Ca2+ imaging. In mouse brain slices, fast-scan cyclic voltammetry was used to measure METH effects on two measures of dopamine: electrically stimulated and DAT-mediated efflux. Intracellular and extracellular Ca2+ was removed through pharmacological blockade of Ca2+ permeable channels (Cd2+ and IP3 sensitive channels), intracellular Ca2+ chelation (BAPTA-AM), or non-inclusion (zero Ca2+). Lastly, METH effects on dopamine-mediated locomotor behavior were tested in rats. Rats received intra-NAc injections of ACSF or 2-aminoethoxydiphenyl borate (2-APB; IP3 receptor blocker) and intraperitoneal METH (5 mg/kg) to test the role of intracellular Ca2+ release in DA-mediated behaviors. RESULTS: Reducing Ca2+ extracellular levels and Ca2+ release from intracellular stores prevented intracellular Ca2+ release. Intracellular Ca2+ chelation and blocking intracellular Ca2+ release reduced METH effects on voltammetric measures of dopamine. Blocking intracellular Ca2+ release via 2-APB resulted in increased METH-induced circling behavior. CONCLUSIONS: METH induces NAc DA release through intracellular Ca2+ activity. Blocking intracellular Ca2+ release prevents METH effects on DA signals and related behavior.
    [Abstract] [Full Text] [Related] [New Search]