Higher magnitude accumbal phasic firing changes among core neurons exhibiting tonic firing increases during cocaine self-administration.
Studies using i.v. cocaine self-administration in rats have documented rapid-phasic changes in the firing rate of nucleus accumbens neurons within seconds of cocaine-reinforced lever presses, as well as changes that occur over the course of the cocaine self-administration experiment, i.e. tonic changes in firing rate. During the self-administration period of the experiment, individual neurons exhibit either a tonic increase, a tonic decrease, or no tonic change in firing rate, relative to the neuron's firing rate during the pre-drug period. We evaluated whether rapid-phasic changes in firing were differentially associated with tonically reduced or tonically elevated firing of nucleus accumbens core and shell neurons in cocaine self-administering rats. Rapid-phasic firing patterns within seconds of the cocaine-reinforced lever press were exhibited predominantly by core neurons that also exhibited tonic increases in firing. Conversely, core neurons that did not exhibit such rapid-phasic firing patterns were more likely to show tonically reduced firing. Moreover, core neurons were more likely than shell neurons to exhibit: 1) tonic increases in firing and 2) rapid-phasic increases in firing preceding the cocaine-reinforced lever press. These differences between accumbens subterritories may be related to their distinct involvement in operant responding; the present findings are consistent with an emerging literature which implicates shell in contextual stimulus-induced responding, and core in processing the instrumental response via its discrete output to classic basal ganglia structures. The distinct tendency of the core to exhibit increased firing, coupled with its dichotomous firing outputs (i.e. tonic decreases without rapid phasic responses or tonic increases with rapid phasic responses), may reflect particular sensitivity of these neurons to excitatory limbic afferent signaling involved in instrumental responding. Enhanced phasic responsivity in the core may be an integral component of the mechanism inherent in normal reward processing which is subverted by chronic drug exposure.
Ghitza
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Behavioral Neuroscience, Clinical Pharmacology and Therapeutics Research Branches, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA.
Prokopenko
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West
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Fabbricatore
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D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003216:Conditioning, Operant / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects; D004594:Electrophysiology; D005793:Generalization, Psychological / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D012055:Reinforcement Schedule; D012646:Self Administration
D000697:Central Nervous System Stimulants; D003042:Cocaine