There are currently no effective pharmacological or behavioral treatments for cocaine addiction. One possible explanation is that the neural correlates of drug-seeking are poorly understood. Understanding the neurophysiology of cocaine-seeking may enable the development of treatments aimed at altering the activity of neurons important for generating these behaviors. One brain region critical for cocaine-seeking behavior is the nucleus accumbens (NAcc). Over the past ten years, our lab has found several correlates of cocaine- seeking encoded by single NAcc neurons during drug and drug-free states. However, cocaine addiction is a complicated disorder that is likely encoded by other brain regions. Since most neurophysiological studies were localized to the NAcc there is a paucity of physiological data supporting this assertion. One region likely to encode cocaine-seeking is the ventral pallidum (VP). The NAcc primarily and massively projects to the VP. Similar to the NAcc, VP lesions decrease cocaine-seeking behavior. However, there has been no neurophysiological investigation into the encoding of cocaine-seeking behavior by VP neurons. In order to address this discrepancy, we will simultaneously record NAcc and VP neurons during cocaine-self administration as well as cocaine-seeking following a period of abstinence in which cocaine-associated cues are noncontingently presented. Such data will be important for understanding the role of VP neurons during binge and relapse behavior. Since the vast majority of NAcc projection neurons are GABAergic (e.g., inhibitory), NAcc neuron firing may be inversely related to VP neuron firing. However, recent reports of VP neurons during sucrose-seeking behavior suggest this may not be the case. The majority of NAcc neurons show increases in firing rate in response to a cocaine predictive cue;a similar majority of VP neurons display increases in firing rate in response to a food predictive cue. A GABAergic inverse relationship of NAcc-VP firing predicts predominant decreases in VP neuron firing in response to cocaine predictive cues. The direction, magnitude, and prevalence of VP subregional neurons during cocaine-seeking behaviors and cue-reactivity will be assessed and compared with previously as well as simultaneously recorded NAcc subregional neurons. Spike triggered averaging of simultaneously recorded NAcc and VP neurons will provide insight into behavior-induced firing patterns. Our preliminary results suggest that VP neurons encode cocaine self-administration behavior heterogenously. Since cocaine addiction is typified by cycles of binging and abstinence, and cues produce cravings, our examination of the neurophysiological correlates of cocaine-seeking and cue-reactivity under drug and abstinent conditions may enable insight into the disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31DA026252-02
Application #
7763794
Study Section
Special Emphasis Panel (ZRG1-F02A-X (20))
Program Officer
Avila, Albert
Project Start
2009-05-25
Project End
2012-05-24
Budget Start
2010-05-25
Budget End
2011-05-24
Support Year
2
Fiscal Year
2010
Total Cost
$32,205
Indirect Cost
Name
Rutgers University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
001912864
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901
Root, David H; Melendez, Roberto I; Zaborszky, Laszlo et al. (2015) The ventral pallidum: Subregion-specific functional anatomy and roles in motivated behaviors. Prog Neurobiol 130:29-70
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
Root, David H; Ma, Sisi; Barker, David J et al. (2013) Differential roles of ventral pallidum subregions during cocaine self-administration behaviors. J Comp Neurol 521:558-88
Ma, Sisi; Pawlak, Anthony P; Cho, Jeiwon et al. (2013) Amphetamine's dose-dependent effects on dorsolateral striatum sensorimotor neuron firing. Behav Brain Res 244:152-61
Root, David H; Fabbricatore, Anthony T; Pawlak, Anthony P et al. (2012) Slow phasic and tonic activity of ventral pallidal neurons during cocaine self-administration. Synapse 66:106-27
Root, David H; Barker, David J; Ma, Sisi et al. (2011) Evidence for learned skill during cocaine self-administration in rats. Psychopharmacology (Berl) 217:91-100
Barker, David J; Root, David H; Ma, Sisi et al. (2010) Dose-dependent differences in short ultrasonic vocalizations emitted by rats during cocaine self-administration. Psychopharmacology (Berl) 211:435-42
Root, David H; Fabbricatore, Anthony T; Ma, Sisi et al. (2010) Rapid phasic activity of ventral pallidal neurons during cocaine self-administration. Synapse 64:704-13
Root, David H; Tang, Chris C; Ma, Sisi et al. (2010) Absence of cue-evoked firing in rat dorsolateral striatum neurons. Behav Brain Res 211:23-32

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