Phasic Firing of Single Neurons in the Rat Nucleus Accumbens Correlated with the Timing of Intravenous Cocaine Self-Administration

Abstract

To examine potential neural mechanisms involved in cocaine self-administration, the activity of single neurons in the nucleus accumbens of rats was recorded during intravenous cocaine self-administration. Lever pressing was reinforced according to a fixed-ratio 1 schedule. On a time base comparable to the interinfusion interval, half the neurons exhibited phasic firing patterns time locked to the cocaine reinforced level press. For almost all neurons, this pattern consisted of a change in firing rate postpress, typically a decrease, followed by a reversal of that change. The postpress change was closely related to the lever press. Typically, it began within the first 0.2 min postpress and culminated within the first 1.0 min postpress. For a small portion of responsive neurons, the reversal of the postpress change was punctate and occurred within 1-3 min of either the last lever press or the next lever press so that firing was stable during much of the interinfusion interval. For the majority of neurons, the reversal was progressive; it began within 2 min after the previous level press, and it was not complete until the last 0.1-2.0 min before the next lever press. The duration of this progressive reversal, but not of the postpress change, was positively correlated with the interinfusion interval. Thus, in addition to exhibiting changes in firing related to the occurrence of self-infusion, the majority of neurons also exhibited progressive changes in firing related to the spacing of infusions. In a structure that has been shown to be necessary for cocaine self-administration, such a firing pattern is a likely neurophysiological component of the mechanism that transduces declining drug levels into increased drug-related appetitive behavior. It is, thus, a neural mechanism that may contribute to compulsive drug-maintained drug taking.

Abstinence from Cocaine Self-Administration Heightens Neural Encoding of Goal-Directed Behaviors in the Accumbens

“…The long-term cyclic alterations reported here are very similar to those shown previously (Peoples and West, 1996). It has been proposed that these long-term discharges may function to translate declining drug levels to increased motivation for the drug and thereby result in increased drug-seeking behavior (Peoples and West, 1996).…”

“…Prior studies have shown that these types of rapid discharges reflect the encoding of associative aspects of the self-administration task (Carelli et al, 1993;Carelli, 2002;Chang et al, 1994;Peoples and West, 1996;Uzwiak et al, 1997). For example, Acb neurons that discharge within seconds before the reinforced response for cocaine appear to encode 'anticipation' of impending drug reward (Carelli et al, 1993;Carelli, 2002;.…”

“…Those studies revealed that, in well-trained animals, a subset of Acb neurons exhibit changes (increases and/or decreases) in firing rate timelocked to lever press responding for intravenous cocaine that occur within two distinct time domains. First, a subset of Acb neurons exhibit rapid changes (increases or decreases) in activity within seconds of lever press responding for cocaine (Carelli et al, 1993;Carelli, 2002;Chang et al, 1994;Peoples and West, 1996;Uzwiak et al, 1997) that appear to reflect associative aspects of the self-administration task. For example, Acb neurons that discharge within seconds before the reinforced response for cocaine appear to encode 'anticipation' of impending drug reward (Carelli et al, 1993;Carelli, 2002;.…”

“…In contrast, Acb neurons that exhibit changes in firing rate within seconds following response completion are related to the association of lever pressing and reward, and are also activated by stimuli paired with drug infusion (Carelli and Ijames, 2001;Carelli, 2000). Second, some Acb neurons exhibit long-term cyclic alterations in cell firing that occur on the order of minutes within the entire interinfusion interval (Peoples and West, 1996;Peoples et al, 1998a, b;Carelli, 2002). It has been proposed that these long-term discharges may be a neurophysiological mechanism that translates declining drug levels to increased motivation for the drug and, consequently, increased drug-seeking behavior (Peoples and West, 1996).…”

“…Second, some Acb neurons exhibit long-term cyclic alterations in cell firing that occur on the order of minutes within the entire interinfusion interval (Peoples and West, 1996;Peoples et al, 1998a, b;Carelli, 2002). It has been proposed that these long-term discharges may be a neurophysiological mechanism that translates declining drug levels to increased motivation for the drug and, consequently, increased drug-seeking behavior (Peoples and West, 1996).…”