A synthetic small-molecule Isoxazole-9 protects against methamphetamine relapse

Abstract

Adult neurogenesis in the dentate gyrus (DG) is strongly influenced by drug taking behavior and may have a role in the etiology of drug seeking behavior. However, mechanistic studies on the relationship of neurogenesis on drug seeking are limited. Outbred Wistar rats experienced extended access methamphetamine self-administration and individual differences in drug taking defined animals with higher preferred and lower preferred levels of drug intake. Forced abstinence from higher preferred levels of drug taking enhanced neurogenesis and neuronal activation of granule cell neurons (GCNs) in the DG and produced compulsive-like drug reinstatement. Systemic treatment with the drug Isoxazole-9 (a synthetic small molecule known to modulate neurogenesis in adult rodent brain) during abstinence blocked compulsive-like context-driven methamphetamine reinstatement. Isoxazole-9 modulated neurogenesis, neuronal activation and structural plasticity of GCNs, and expression of synaptic proteins associated with learning and memory in the DG. These findings identify a subset of newly born GCNs within the DG that could directly contribute to drug-seeking behavior. Taken together, these results support a direct role for the importance of adult neurogenesis during abstinence in compulsive-like drug reinstatement.

Abstinence from prolonged ethanol exposure affects plasma corticosterone, glucocorticoid receptor signaling and stress-related behaviors

“…Separate aliquots of mPFC tissue was used in this study to measure tGR and pGR ser211 levels and have never been published previously (Experiment 8). An additional cohort of ethanol naïve rats were trained to self-administer saline (n=4) in identical operant conditioning paradigm (behavior data presented in (Galinato et al, 2017)); plasma from these rats were collected prior to abstinence from self-administration to determine peak CORT levels in ethanol naïve but behaviorally trained rats.…”

“…These rats were also subjected to forced abstinence from saline self-administration and followed by extinction and cue-induced reinstatement. The self-administration data for these saline rats are presented elsewhere (Galinato et al, 2017). Thus, these rats were behaviorally trained, but ethanol-naïve.…”

The neurobiological mechanisms of physical exercise in methamphetamine addiction

“…Importantly, a robust rebound in neurogenesis was associated with enhanced propensity for reinstatement during METH abstinence in METH self‐administered rats . Moreover, forced abstinence from higher preferred levels of METH intake enhanced neurogenesis and neuronal activation of granule cell neurons (GCNs) in the DG and produced compulsive‐like drug reinstatement in rats . Furthermore, systemic treatment with the drug isoxazole‐9 (a synthetic small molecule known to modulate neurogenesis in the adult rodent brain) during abstinence blocked compulsive‐like context‐driven methamphetamine reinstatement .…”

Strategies for the Development of Metallic‐Nanoparticle‐Based Label‐Free Biosensors and Their Biomedical Applications

“…Using it in higher concentrations can cause the failure of skeletal muscles, stroke, and other physiological diseases, ultimately leading to death. Therefore, the detection of such drugs is vital to save human lives . This analysis was performed by mixing saliva samples and iodide‐modified silver colloids before loading them into the microfluidic device.…”