[Show abstract][Hide abstract] ABSTRACT: Repeated, extreme, or traumatic stressors can elicit pathological effects leading to many negative physical and psychological outcomes. Stressors can precipitate the onset of psychiatric diseases, or exacerbate pre-existing disorders including various anxiety and mood disorders. As stressors can negatively impact human psychiatric health, it is essential to identify neurochemicals that may confer protection from the negative sequelae of repeated or extreme stress exposure. Elucidating the neurobiological underpinnings of stress resilience will enhance our ability to promote resilience to, or recovery from, stress-related psychiatric disease. Herein, we will review the evidence for neuropeptide Y as an endogenous mediator of resilience and its potential relevance for the treatment of stress-related psychiatric diseases.
[Show abstract][Hide abstract] ABSTRACT: Posttraumatic stress disorder (PTSD) co-occurs highly with substance use disorders (SUD), yet the neurobiological basis for this comorbid relationship remains unclear. PTSD and SUDs result in similar pathological states including impulsive behavior, reward deficiency, and heightened stress sensitivity. Hence, PTSD and SUD may depend on overlapping dysfunctional neurocircuitry. Here we provide a short overview of the relationship between comorbid PTSD and SUD, as well as the potential role of select neurotransmitter systems that may underlie enhanced vulnerability to drug abuse in the context of PTSD.
No preview · Article · Dec 2013 · Pharmacology Biochemistry and Behavior
[Show abstract][Hide abstract] ABSTRACT: Heightened anxiety and sensitivity to stress following chronic cocaine use are likely to increase an individual's susceptibility for relapse to drug-seeking behavior. Thus, it is important to investigate the neural mechanisms responsible for the regulation of anxiety during cocaine withdrawal and stress-induced relapse in order to identify potential targets for pharmacological intervention. This chapter will address the involvement of several neurotransmitter systems in regulating anxiety during cocaine withdrawal and stress-induced relapse mechanisms. The distinct roles of the dopamine, serotonin, corticotropin releasing factor, norepinephrine, and opioid systems in regulating the negative consequences of cocaine withdrawal and the effects of stress in eliciting relapse to drug use will be discussed. In addition, a section detailing the potential role of other neuropeptides like cholecystokinin and neuropeptide Y in cocaine withdrawal-induced anxiety and stress-induced relapse is included. It is important to consider the roles of these brain-signaling systems separately, as well as integrated in a network that functions in regulating anxiety during cocaine withdrawal and the effects of stress on drug abuse and relapse to drug use. By targeting these regulatory mechanisms, potential pharmacological targets may be identified in support of the prevention of relapse to drug use.
[Show abstract][Hide abstract] ABSTRACT: Glycogen synthase kinase 3 (GSK3) is implicated in mediating dopamine-dependent behaviors. Previous studies have demonstrated the ability of amphetamine, which increases extracellular dopamine levels and influences behavior, to regulate the activity of GSK3. This study used valproic acid and the selective GSK3 inhibitor, SB 216763, to examine the role of GSK3 in amphetamine-induced hyperactivity and the development of sensitized stereotypic behavior. Pretreatment with valproic acid (50-300 mg/kg, i.p.) or SB 216763 (2.5-5 mg/kg, i.p.) prior to amphetamine (2 mg/kg, i.p.) significantly reduced amphetamineinduced ambulation and stereotypy. To assess the development of sensitization to the stereotypic effects of amphetamine, mice were pretreated daily with valproic acid (300 mg/kg) or SB 216763 (5 mg/kg) prior to amphetamine (2 mg/kg) for 5 days. Upon amphetamine challenge (1 mg/kg) 7 days later, mice pretreated with valproate or SB 216763 showed a significant attenuation of amphetamine-induced sensitization of stereotypy. To determine whether regulation of GSK3 activity was associated with attenuation of acute amphetamine-induced hyperactivity by valproic acid, valproate (300 mg/kg) or vehicle was injected prior to amphetamine (2 mg/kg) or saline and brain tissue obtained. Analysis of the levels of phospho-GSK3α and β by immunoblot indicated that valproate increased phosphorylation of ser²¹-GSK3α in the frontal cortex, as well as ser⁹-GSK3β in the frontal cortex and caudate putamen of amphetamine-injected mice. These data support a role for GSK3 in acute amphetamine-induced hyperactivity and the development of sensitization to amphetamine-induced stereotypy.
Preview · Article · May 2012 · Behavioural brain research