Phasic Firing Time Locked to Cocaine Self-Infusion and Locomotion: Dissociable Firing Patterns of Single Nucleus Accumbens Neurons in the Rat

Abstract

The activity of single nucleus accumbens (NAcc) neurons of rats was extracellularly recorded during intravenous cocaine self-administration sessions (0.7 mg/kg per infusion, fixed ratio 1). We reported previously that NAcc neurons showed a change, usually a decrease, in firing rate during the first 1 min after the cocaine-reinforced lever press. This postpress change was followed by a progressive reversal of that change, which began within the first 2 min after the press and was not complete until the last 1 min before the next lever press (termed the change + progressive reversal firing pattern). In the present study we documented a regular pattern of locomotion that occurred in parallel with the change + progressive reversal firing pattern. This observation suggested that discharges time locked to locomotion may determine the change + progressive reversal firing pattern. However, 55% of the neurons failed to show firing time locked to locomotion that could have contributed to the change + progressive reversal firing pattern. Moreover, for all neurons, the change + progressive reversal firing pattern was apparent even if the calculation of firing rate excluded all periods of locomotion. The present data showed that the change + progressive reversal firing pattern is not solely attributable to phasic changes in firing time locked to the execution of locomotion. The change + progressive reversal firing pattern closely mirrors changes in drug level and dopamine overflow observed by previous researchers and may thus be a component of the neurophysiological mechanism by which drug level regulates drug-taking behavior during an ongoing self-administration session.

Differences Between Accumbens Core and Shell Neurons Exhibiting Phasic Firing Patterns Related to Drug-Seeking Behavior During a Discriminative-Stimulus Task

“…On the final training session, the mean percentage of tone presentations during which rats lever pressed was 96.2 Ϯ 2.1%. By the end of tone discrimination training, all rats self-administered levels of cocaine that remained stable throughout the session at ϳ2-3 mg/kg calculated blood level of drug; this drug level was lower than that observed in a FR1 schedule (Peoples et al , 1999a. During the reinstatement session, all rats engaged in reinstatement of drug-seeking behavior and maintained a 2-3 mg/kg calculated blood level of drug.…”

“…B: example of a shell neuron exhibiting a postpress decrease in firing, which was the most common among shell postpress firing patterns. C 1 and C 2 : example of a single shell neuron (meeting all criteria of Peoples et al 1999a) exhibiting similar firing patterns around the unreinforced lever presses in both extinction (C 2 ) and reinstatement (C 1 ) as evidenced by similar B/(A ϩ B) values under both conditions (0.27 for C 1 and 0.32 for C 2 , both values reflecting a postpress decrease in firing; 0.67 for C 1 and 0.71 for C 2 , both values reflecting a prepress increase in firing). Figs.…”

“…Among core neurons, this change in firing was the most common among postpress firing patterns. C 1 and C 2 : example of a single core neuron (meeting all criteria of Peoples et al 1999a) exhibiting similar firing patterns in both extinction and reinstatement as evidenced by similar B/(A ϩ B) values (0.64 for C 1 and 0.66 for C 2 ) under both conditions. The greater number of discharges in the raster of C 2 than in the raster of C 1 reflects the greater number of unreinforced lever presses made by the animal during reinstatement (C 2 ) than during extinction (C 1 ).…”

Behavioral functions of the mesolimbic dopaminergic system: An affective neuroethological perspective

“…DA release generally depresses spontaneous and evoked cell firing (Siggins, 1978;Dray, 1980;Rowlands & Roberts, 1980;Yim & Mogenson, 1982;1986;Brown & Arbuthnott, 1983;Johnson et al, 1983;Yang & Mogenson, 1984;DeFrance et al, 1985;Chiodo & Berger, 1986;Hu & Wang, 1988;Nisenbaum et al, 1988;Hu et al, 1990;Pennartz et al, 1992;Harvey & Lacey, 1996;Nicola et al, 1996;Peoples & West, 1996;Peoples et al, 1998;Nicola & Deadwyler, 2000;Zhang et al, 2002). It has been argued that behavioral arousal emerges from a DA disinhibitory role obtained by the block of an inhibitory pathway.…”

Accumbal Neurons that are Activated during Cocaine Self-Administration are Spared from Inhibitory Effects of Repeated Cocaine Self-Administration

“…The time points included the following: (1) the 30 s pre-S D (ie measure of basal firing), (2) the 30 s post-S D , (3) the 30 s pre-1st-press, (4) the 30 s post-1st-press, and (5) the 30-s pre-press period during which the median pre-press firing rate for presses 20-30 was achieved (see Peoples et al, 1998aPeoples et al, , 2004Peoples and Cavanaugh, 2003). The firing rates during these periods were subjected to an ANOVA (two-tailed, a ¼ 0.05).…”