The development of effective behavioral or pharmacological treatments for cocaine dependence relies on increasing our understanding of the behavioral and neural correlates of drug-seeking. Positive and negative affective states both have a reported role in the initiation of drug use (Newcomb &Felix-Ortiz 1992), bingeing behavior (Barker et al., 2010;Maier et al., 2010), withdrawal (Covington &Miczek 2003;Barros &Miczek 1996;Mutschler &Miczek 1998a;Mutschler &Miczek 1998b), or relapse (Hodgins et al., 1995). Still, studies investigating the neurobiological correlates of affect and the role affect plays in drug dependence are limited. Over the last fifteen years, the hypothesis that the affective states of rats can be reliably indexed through ultrasonic vocalizations (USVs) has received much support;50-kHz USVs and 22-kHz USVs are consistently reported to be correlated with indices of positive and negative affective states, respectively, in adult rats in a variety of experimental paradigms. Incorporating USVs with self-administration behavior would therefore allow for a more comprehensive animal model of addiction. Preliminary results from our lab (Barker et al., 2010) suggest that doses of cocaine that prevent drug 'satiety'produce a higher ratio of negative affective USVs while those that allow animals to reach their preferred blood concentration produce a higher ratio of positive affective USVs. Research examining the neurochemistry of USV production has suggested that two separate but overlapping systems modulate 22- and 50-kHz USVs, respectively. The first of these systems-the mesolimbic dopamine system-has a purported role in the modulation of 50-kHz USVs. On the other hand, 22-kHz USVs are thought to be modulated by a second, cholinergic circuit originating in the laterodorsal tegmental nucleus (Brudzynski, 2008). One key region of overlap between these systems is the nucleus accumbens. Appropriately, eletrophysiological and neurochemical evidence has also implicated the NAcc in processing appetitive and aversive outcomes (e.g. Wheeler et al., 2008) as well as facilitating approach and avoidance behaviors (e.g. Rada &Hoebel, 2001;Hoebel, Avena, &Rada, 2007) To further investigate the neural substrates of affective processing during self-administration, as well as the role that affect plays in the reinstatement of drug-seeking behavior, we will record ultrasonic vocalizations, and the firing of NAcc core and medial shell neurons during a zero dose saline condition, two self-administered cocaine doses, and tests of reinstatement.
The proposed research is in line with NIDA's strategies for the prevention of drug use and prevention of escalated intake in current substance users. Specifically, the project serves to inform our understanding of the neurobiological substrates of affect and provide insight into the role affect may play in influencing the brain circuitry involved in the initiation of drug use, bingeing, withdrawal, and relapse.
|Barker, David J; Simmons, Steven J; West, Mark O (2015) Ultrasonic Vocalizations as a Measure of Affect in Preclinical Models of Drug Abuse: A Review of Current Findings. Curr Neuropharmacol 13:193-210|
|Barker, David J; Striano, Brendan M; Coffey, Kevin C et al. (2015) Sensitivity to self-administered cocaine within the lateral preoptic-rostral lateral hypothalamic continuum. Brain Struct Funct 220:1841-54|
|Coffey, Kevin R; Barker, David J; Gayliard, Nick et al. (2015) Electrophysiological evidence of alterations to the nucleus accumbens and dorsolateral striatum during chronic cocaine self-administration. Eur J Neurosci 41:1538-52|
|Striano, Brendan M; Barker, David J; Pawlak, Anthony P et al. (2014) Olfactory tubercle neurons exhibit slow-phasic firing patterns during cocaine self-administration. Synapse 68:321-3|
|Barker, David J; Herrera, Christopher; West, Mark O (2014) Automated detection of 50-kHz ultrasonic vocalizations using template matching in XBAT. J Neurosci Methods 236:68-75|
|Barker, David J; Bercovicz, Danielle; Servilio, Lisa C et al. (2014) Rat ultrasonic vocalizations demonstrate that the motivation to contextually reinstate cocaine-seeking behavior does not necessarily involve a hedonic response. Addict Biol 19:781-90|
|Barker, David J; Simmons, Steven J; Servilio, Lisa C et al. (2014) Ultrasonic vocalizations: evidence for an affective opponent process during cocaine self-administration. Psychopharmacology (Berl) 231:909-18|
|Barker, David J; Root, David H; Coffey, Kevin R et al. (2014) A procedure for implanting organized arrays of microwires for single-unit recordings in awake, behaving animals. J Vis Exp :e51004|
|Coffey, Kevin R; Barker, David J; Ma, Sisi et al. (2013) Building an open-source robotic stereotaxic instrument. J Vis Exp :e51006|
|Coffey, Kevin R; Barker, David J; Ma, Sisi et al. (2013) Effects of varying reinforcement probability on pavlovian approach behavior and ultrasonic vocalizations in rats. Behav Brain Res 237:256-62|
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