Background: Betaine is a functional nutrient with a variety of potential health benefits1.2. It has been shown to attenuate the reinstatement of ketamine-seeking behavior in rats3. Moreover, betaine activates AMP-activated protein kinase (AMPK) and functions as a partial agonist of the NMDA receptor glycine binding site, both of which have been associated with reducing cue-induced reinstatement4.5.6. Aims & Objectives: The study aimed to both identify the brain regions associated with betaine's reduction effect on cue-induced reinstatement of ketamine seeking and to explore the involvement of NMDA receptor and AMPK in the potential underlying mechanisms. Methods: Male Sprague-Dawley rats were trained to respond for intravenous ketamine (0.5 mg/kg/infusion) self-administration, followed by extinction. Prior to cue-induced reinstatement, rats received bilateral microinjection of betaine (100 μ g/μ l/side) either into the prelimbic cortex (PrL) or the nucleus accumbens (NAc) core. The impact of pretreatment of 7-chlorokynurenate (7-CK) (20 μ g/μ l/side), an antagonist of NMDA receptor glycine binding site, or dorsomorphin (6 μ g/μ l/side), an AMP-activated protein kinase (AMPK) inhibitor, on betaine's effects in the NAc core regarding cue-induced reinstatement were examined. Results: Our data demonstrated a significant reduction in cue-induced reinstatement of ketamine-seeking behavior when betaine was administered into the NAc core, with no such effect observed in the PrL. In addition, dorsomorphin, but not 7-CK, blocked the effect of betaine on cue-induced reinstatement of ketamine- seeking behavior. Discussion & Conclusions: These findings suggest the potential benefits of betaine supplementation for individuals with ketamine use disorder. Moreover, it sheds light on betaine's capacity to mitigate cue-induced reinstatement of ketamine-seeking behavior by activating AMPK in the NAc core.
Date:
2025-02-12
Relation:
International Journal of Neuropsychopharmacology. 2025 Feb 12;28(Suppl. 1):i308-i309.
