Electrophysiological evidence of mediolateral functional dichotomy in the rat nucleus accumbens during cocaine self‐administration II: phasic firing patterns

Abstract

In the cocaine self-administering rat, individual nucleus accumbens (NAcc) neurons exhibit phasic changes in firing rate within minutes and/or seconds of lever presses (i.e. slow phasic and rapid phasic changes, respectively). To determine whether neurons that demonstrate these changes during self-administration sessions are differentially distributed in the NAcc, rats were implanted with jugular catheters and microwire arrays in different NAcc subregions (Core, Dorsal Shell, Ventromedial Shell, Ventrolateral Shell or Rostral Pole). Neural recording sessions were typically conducted on Day 13 -17 of cocaine self-administration (0.77 mg/kg/0.2mL infusion; fixed-ratio 1 schedule of reinforcement; 6 hr daily sessions). Pre-press rapid phasic firing rate changes were greater in lateral accumbal (core, ventrolateral shell) relative to medial accumbal (dorsal shell, rostral pole shell) subregions. Slow phasic pattern analysis revealed that reversal latencies of neurons that exhibited change + reversal patterns differed mediolaterally: medial NAcc neurons exhibited more early reversals and fewer progressive/late reversals than lateral NAcc neurons. Comparisons of firing patterns within individual neurons across time bases indicated that lateral NAcc pre-press rapid phasic increases were correlated with tonic increases. Tonic decreases were correlated with slow phasic patterns in individual medial NAcc neurons, indicative of greater pharmacological sensitivity of neurons in this region. On the other hand, the bias of the lateral NAcc towards increased pre-press rapid phasic activity coupled with a greater prevalence of tonic increase firing may reflect particular sensitivity of these neurons to excitatory afferent signaling and perhaps differential pharmacological influences on firing rates between regions. Keywords addiction; drug abuse; neurophysiology; reward; ventral striatumThe nucleus accumbens' (NAcc) putative role in reward and drug-taking behavior has prompted numerous studies in recent years that measured various physiological changes in the NAcc during drug self-administration. Several laboratories have investigated whether NAcc neural firing patterns during cocaine self-administration are temporally linked to events such as drug infusion or appetitive behavior (Carelli et al, 1993;Chang et al, 1994;Peoples & West, 1996, Woodward et al, 1999Carelli, 2002). Two main categories of lever press-related firing patterns have been identified: slow phasic and rapid phasic.* Correspondence to: Anthony T. Fabbricatore, Ph.D., Rutgers, the State University of NJ, Department of Psychology, 152 Frelinghuysen Road, Piscataway, NJ 08854, Phone: (732) Fax: (732) 445-2263, tonio@rci.rutgers.edu. Dr. Ghitza's current affiliation: Center for the Clinical Trials Network, National Institute on Drug Abuse (NIDA) National Institutes of Health (NIH), Bethesda, Maryland, USA. NIH Public Access Author ManuscriptEur J Neurosci. Author manuscript; available in PMC 2011 May 1. NIH-PA Author ManuscriptNIH-PA Author Manuscr...

Slow phasic and tonic activity of ventral pallidal neurons during cocaine self‐administration

“…Previous analyses of NAcc slow phasic firing patterns in this laboratory (Peoples and West, 1996; Peoples et al 1998; Fabbricatore et al 2010) have defined two types of post-press changes (increase and decrease), both with three different kinds of reversal patterns (early, progressive, and late). A new slow phasic assessment procedure, which included the PCA based categorization, was developed for the present study.…”

“…While the schedule of reinforcement used was a 40 second fixed interval, responses during cocaine self-administration are regulated by the intravenous dose (Pickens and Thompson, 1968). The dose used in the current study generates inter-response intervals between 6 and 8 min (Peoples and West, 1996; Peoples et al 1998; Fabbricatore et al 2010). Prior to recordings, all self-administration sessions were six hours in duration or 80 infusions were earned, whichever occurred first.…”

“…All other reinforced lever presses were analyzed, which averaged 41.27 ± 0.39 reinforced presses per session. Data for slow-phasic changes in firing were determined by constructing rasters and PETHs that displayed neuronal discharges (spikes/sec) within ± 4 min of each lever press (12 sec bin width) (Peoples and West, 1996; Peoples et al 1998; Fabbricatore et al 2010). Trials in which the inter-infusion interval was less than four minutes occurred in only 3.03% of all nodes.…”

Multiplexed neurochemical signaling by neurons of the ventral tegmental area

“…Although the extent to which these mesoaccumbens DA-glutamate fibers participate in the neurobiology of drugs of abuse remains to be determined, we speculate that these axons may participate in the regulation of neuronal activity in cocaine self-administration. Specifically, electrophysiological recordings have shown that nAcc neurons exhibit rapid phasic firing patterns to related cues and actions to obtain the drug (Peoples et al, 1998; Ghitza et al, 2003, 2004, 2006; Fabbricatore et al, 2009, 2010; Coffey and Barker et al, 2015). The nAcc neurons also exhibit slow-phasic and tonic changes in firing rate that correlate with the pharmacological effects of cocaine, and do not correlate with the rapid phasic firing patterns (Fabbricatore et al, 2010).…”

“…Specifically, electrophysiological recordings have shown that nAcc neurons exhibit rapid phasic firing patterns to related cues and actions to obtain the drug (Peoples et al, 1998; Ghitza et al, 2003, 2004, 2006; Fabbricatore et al, 2009, 2010; Coffey and Barker et al, 2015). The nAcc neurons also exhibit slow-phasic and tonic changes in firing rate that correlate with the pharmacological effects of cocaine, and do not correlate with the rapid phasic firing patterns (Fabbricatore et al, 2010). Furthermore, slow phasic pharmacologic and rapid phasic behavioral firing patterns are similarly processed in downstream accumbal targets (ventral pallidum and lateral preoptic area; Root et al, 2012, 2013; Barker et al, 2014).…”