Glutamate homeostasis and dopamine signaling: Implications for psychostimulant addiction behavior. (March 2021)

• Record Type: Journal Article
• Authors: Fischer, Kathryn D.; Knackstedt, Lori A.; Rosenberg, Paul A.
• Is Part Of: Neurochemistry international. Volume 144(2021)
• Publication Date: 2021-03
• Subjects: Transport -- Uptake -- Co-transmission -- Cre-recombinase -- Nucleus accumbens -- Ventral tegmental area; GLU glutamate -- DA dopamine -- NAc nucleus accumbens -- VTA ventral tegmental area -- PFC prefrontal cortex -- METH methamphetamine -- AMP amphetamine -- mGluR metabotropic glutamate receptor -- NAC N-acetylcysteine -- IVSA Intravenous Self-Administration -- CPP Conditioned Place Preference; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2020.104896
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: Cocaine, amphetamine, and methamphetamine abuse disorders are serious worldwide health problems. To date, there are no FDA-approved medications for the treatment of these disorders. Elucidation of the biochemical underpinnings contributing to psychostimulant addiction is critical for the development of effective therapies. Excitatory signaling and glutamate homeostasis are well known pathophysiological substrates underlying addiction-related behaviors spanning multiple types of psychostimulants. To alleviate relapse behavior to psychostimulants, considerable interest has focused on GLT-1, the major glutamate transporter in the brain. While many brain regions are implicated in addiction behavior, this review focuses on two regions well known for their role in mediating the effects of cocaine and amphetamines, namely the nucleus accumbens (NAc) and the ventral tegmental area (VTA). In addition, because many investigators have utilized Cre-driver lines to selectively control gene expression in defined cell populations relevant for psychostimulant addiction, we discuss potential off-target effects of Cre-recombinase that should be considered in the design and interpretation of such experiments. Highlights: METH, AMP, and cocaine alter glutamate homeostasis within the mesolimbic circuit. GLT-1 and xCT are the glutamate transporters primarily responsible for addiction related changes in glutamate homeostasis. GLT-1 and xCT are therapeutic targets for METH, AMP, and cocaine addiction behaviors. Glutamate co-transmission by dopamine neurons is important for behavioral responses to psychostimulants.