Articles: nucleus-accumbens-drug-effects.
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Biological psychiatry · Dec 2019
Dopamine D1 and D2 Receptors Differentially Regulate Rac1 and Cdc42 Signaling in the Nucleus Accumbens to Modulate Behavioral and Structural Plasticity After Repeated Methamphetamine Treatment.
Methamphetamine (METH) is a highly addictive psychostimulant that strongly activates dopamine receptor signaling in the nucleus accumbens (NAc). However, how dopamine D1 and D2 receptors (D1Rs and D2Rs, respectively) as well as downstream signaling pathways, such as those involving Rac1 and Cdc42, modulate METH-induced behavioral and structural plasticity is largely unknown. ⋯ D1Rs and D2Rs differentially regulate Rac1 and Cdc42 signaling to modulate METH-induced behavioral plasticity and the structural remodeling of medium spiny neurons in the NAc.
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Growing research indicates oxytocin may be involved in relieving anxiety and attenuating the rewarding effects of psychostimulants. This study investigated the effects of subchronic oxytocin treatments on mesolimbic dopamine transmission in areas associated with anxiety and addiction, the amygdala and the nucleus accumbens (NAc), respectively. Using in vivo fixed potential amperometry, stimulation-evoked dopamine release was recorded in anesthetized mice pretreated with subchronic oxytocin (four i.p. injections of 1 mg/kg oxytocin or saline with 48 h between injections). ⋯ Furthermore, oxytocin pretreated mice displayed a reduced dopaminergic response to the drug challenge of nomifensine relative to control mice. Together these results suggest that oxytocin may be useful at treating aspects of anxiety and drug abuse. Elucidating the neural effects of oxytocin is critical given the multitude of potential therapeutic uses for this drug.
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Astrocytes provide support for neurons, regulate metabolic processes, and influence neuronal communication in a variety of ways, including through the homeostatic regulation of glutamate. Following 2-h cocaine or methamphetamine self-administration (SA) and extinction, rodents display decreased levels of basal glutamate in the nucleus accumbens core (NAcore), which transitions to elevated glutamate levels during drug seeking. We hypothesized that, like cocaine, this glutamate 'overflow' during methamphetamine seeking arises via decreased expression of the astroglial glutamate transporter GLT-1, and withdrawal of perisynaptic astroglial processes (PAPs) from synapses. ⋯ In order to test the impact of astrocyte activation and the induction of glial glutamate release within the NAcore, we employed astrocyte-specific expression of designer receptors exclusively activated by designer drugs (DREADDs). We show here that acute activation of Gq-coupled DREADDs in this region inhibited cued methamphetamine seeking. Taken together, these data indicate that cued methamphetamine seeking following two-hour SA is not mediated by deficient glutamate clearance in the NAcore, yet can be inhibited by engaging NAcore astrocytes.
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Adolescent binge drinking renders young drinkers vulnerable to alcohol use disorders in adulthood; therefore, understanding alcohol-induced brain damage and associated cognitive dysfunctions is of paramount importance. Here we investigated the effects of binge-like adolescent intermittent ethanol (AIE) exposure on nonspatial working memory, behavioral flexibility and cholinergic alterations in the nucleus accumbens (NAc) in male and female rats. On postnatal days P25-57 rats were intubated with water or ethanol (at a dose of 5 g/kg) on a 2-day-on/2-day-off cycle and were then tested in adulthood on social recognition and probabilistic reversal learning tasks. ⋯ During probabilistic reversal learning, AIE-treated male and female rats showed behavioral inflexibility as indicated by a higher number of trials needed to complete three reversals within a session, longer response latencies for lever selection, and for males, a higher number of errors as compared to water-treated rats. AIE exposure also reduced the number of cholinergic interneurons in the NAc in males and females. These findings indicate AIE-related pathologies of accumbal cholinergic interneurons and long lasting cognitive-behavioral deficits, which may be associated with cortico-striatal hypofunction.
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Case Reports
Deep Brain Stimulation of Nucleus Accumbens for Methamphetamine Addiction: Two Case Reports.
Methamphetamine (MA) addiction is one of the most prevalent socioeconomic and health problems worldwide. In recent years, deep brain stimulation (DBS) has increasingly been used for the treatment of addiction. ⋯ These case reports demonstrate that NAc-DBS maybe a possible treatment option for MA addiction.