Learning to inhibit drug seeking can be an important strategy for inhibiting relapse, and this modeled by extinguishing in response a drug-paired context. Rats were either extinguished or withdrawn without extinction training (abstinence) from cocaine self-administration, measurements of postsynaptic density proteins the core shell subcompartments nucleus accumbens compared with yoked-saline controls. Only rats had elevations PSD-95, Homer1b/c, Narp core, whereas no measured altered...

Abstract Both pre‐clinical and clinical studies indicate that N ‐acetylcysteine ( NAC ) may be useful in treating relapse to addictive drug use. Cocaine self‐administration rats reduces both cystine‐glutamate exchange glutamate transport via GLT ‐1 the nucleus accumbens, treatment normalizes these two glial processes critical for maintaining homeostasis. However, it is not known if one or of actions by needed inhibit cocaine seeking. To determine whether restoration and/or required...

Decreased basal glutamate levels are observed in the rat nucleus accumbens (NA) core following cocaine self-administration. This disruption of homeostasis arises from a reduction export via system x C − and is accompanied by decrease expression xCT, catalytic subunit . A second hallmark disrupted function major transporter, GLT-1. We have previously shown that chronic treatment with antibiotic ceftriaxone restores xCT GLT-1 self-administration attenuates both cue- cocaine-primed...

Cocaine addicts increase the frequency and amount of drug use over time. This characteristic has been modeled by escalating intake in rats that were given extended access to cocaine. However, it remains unclear whether behavior or simply increased dose is relevant aspect this model. The present study investigated phenomenon escalated drug-taking enhances cocaine-induced sensitization reinstatement. Rats trained self-administer cocaine during daily 1-h sessions for 7 days. A short-access...

ABSTRACT In animal models of addiction, reducing glutamate stimulation the metabotropic receptor 5 (mGluR5) inhibits drug‐seeking. The present study used reinstatement model cocaine‐seeking to show that blockade mGluR5 directly in core subcompartment nucleus accumbens (NAcore) prevented both conditioned cue‐ and cocaine‐reinstated Consistent with this finding, microinjection agonist (RS)‐2‐chloro‐5‐hydroxyphenylglycine into NAcore produced modest lever pressing when given alone significantly...

Long-term treatment with ceftriaxone attenuates the reinstatement of cocaine seeking while increasing function glutamate transporter 1 (GLT-1) and system xC- (Sxc) in nucleus accumbens core (NAc). Sxc contributes majority nonsynaptic extracellular NAc, GLT-1 is responsible for uptake. Here we used antisense to decrease expression xCT (a catalytic subunit Sxc) determine relative importance both proteins mediating ability prevent cue-induced normalize glutamatergic NAc rats. Intra-NAc...

Cocaine addiction is a chronic, relapsing disease characterized by an inability to regulate drug-seeking behavior. Here we investigated the role of mGluR5 in ventral and dorsal striatum regulating cocaine-seeking following both abstinence extinction. Animals underwent 2 weeks cocaine self-administration followed 3 home-cage abstinence. were then reintroduced operant chamber for context-induced relapse test, 7–10 days extinction training. Once responding was extinguished, cue-primed...

Abstract PTSD is highly comorbid with cocaine use disorder (CUD), and users + CUD are more resistant to treatment. Here we sought develop a rat model of in order identify the neurobiological changes underlying such comorbidity screen potential medications for reducing seeking population. We utilized predator scent stress PTSD, wherein rats received single exposure fox pheromone 2,5-dihydro-2,4,5-trimethylthiazoline (TMT). One week after TMT exposure, stress-susceptible (susceptible),...

Post-traumatic stress disorder (PTSD) currently has no FDA-approved treatments that reduce symptoms in the majority of patients. The ability to extinguish fear memory associations is impaired PTSD individuals. As such, development extinction-enhancing pharmacological agents be used combination with exposure therapies may benefit treatment PTSD. Both mGlu5 and CB1 receptors have been implicated contextual extinction. Thus, here we tested positive allosteric modulator...

Repeated cycles of chronic intermittent ethanol (CIE) exposure increase voluntary consumption in mice. Previous work has shown that extracellular glutamate the nucleus accumbens (NAc) is significantly elevated ethanol-dependent mice and pharmacologically manipulating concentrations NAc will alter drinking, indicating homeostasis plays a crucial role drinking this model. The present studies were designed to measure at time point which would ordinarily be allowed access CIE model and,...

Oxytocin reduces cued reinstatement of cocaine seeking in male and female rats, but the underlying neurobiology has not been uncovered. The majority effort on this task focused oxytocin dopamine interactions nucleus accumbens core. core is a key neural substrate relapse, administration to methamphetamine cues. Further, strong glutamatergic innervation from numerous regions including prefrontal cortex. Thus, we hypothesize that regulates presynaptic glutamate terminals core, thereby affecting...

Glutamate neurotransmission in the nucleus accumbens core (NAc) mediates ethanol consumption. Previous studies using non-contingent and voluntary alcohol administration inbred rodents have reported increased basal extracellular glutamate levels NAc. Here, we assessed NAc following intermittent consumption male Sprague-Dawley rats that had access to for 7 weeks on alternating days. We found at 24 h withdrawal from thus sought identify source of this glutamate. To do so, employed a combination...