Research into the neural bases of cocaine abuse has established an essential role of the mesolimbic dopamine (DA) system innervating the nucleus accumbens (NAc). Recently, the nigrostriatal DA system innervating the dorsolateral striatum (DLS), a region necessary for acquiring habits, has been implicated in cocaine abuse. According to this view, drug self- administration gradually recruits striatal circuitry beyond the ventromedial striatum (accumbens), eventually spreading to the DLS. Rats will self-administer cocaine in a tone discrimination task, 6 hours/day, 7 days a week for 4 weeks to model both the long access/escalation pattern of intake described by Ahmed and Koob (1998) and the accompanying changes in striatum that have been shown to occur in the chronically drug-exposed brain by Porrino et al. (2004). Among numerous single unit recording studies during cocaine self-administration in well trained subjects, none have ever i) recorded DLS neurons, ii) recorded NAc shell, core and DLS simultaneously, or iii) tracked their phasic firing patterns from the first session throughout an extended period of cocaine self-administration. All three are the focus of the proposed studies. The instrumental response will be a vertical head movement or licking a dry spout, in order to target DLS neurons related specifically to one of those two movements. Single unit activity will be recorded simultaneously from NAc medial shell and core neurons, from non-sensorimotor DLS neurons and from DLS neurons related specifically to vertical head movement or to licking. Single neurons will be tracked across sessions to assess changes within and between subregions. The spatial and temporal resolution of the proposed single unit recordings would bring an unprecedented level of detail to the tracking of long-term neural changes associated with chronic cocaine abuse, and assure the acquisition of new and valuable information that will be necessary ultimately for mechanistic explanations.

Public Health Relevance

Chronic cocaine self-administration causes changes in circuitry of the human basal ganglia. Rats will self-administer cocaine in a long access/escalation pattern to model these reported changes. Single neuron impulse activity will be tracked across self-administration sessions to assess changes in rat basal ganglia circuits. The spatial and temporal resolution of single unit recordings would provide valuable information relevant to mechanistic explanations of long-term neural changes associated with chronic cocaine abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA006886-18
Application #
8469840
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Volman, Susan
Project Start
1991-05-01
Project End
2016-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
18
Fiscal Year
2013
Total Cost
$290,948
Indirect Cost
$98,948
Name
Rutgers University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
001912864
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901
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
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; 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; 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; 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
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
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
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
Coffey, Kevin R; Barker, David J; Ma, Sisi et al. (2013) Building an open-source robotic stereotaxic instrument. J Vis Exp :e51006
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

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