Abstinence from cocaine and sucrose self-administration reveals altered mesocorticolimbic circuit connectivity by resting state MRI.

Previous preclinical studies have emphasized that drugs of abuse, through actions within and between mesocorticolimbic (MCL) regions, usurp learning and memory processes normally involved in the pursuit of natural rewards. To distinguish MCL circuit pathobiological neuroadaptations that accompany addiction from general learning processes associated with natural reward, we trained two groups of rats to self-administer either cocaine (IV) or sucrose (orally) followed by an identically enforced 30 day abstinence period. These procedures are known to induce behavioral changes and neuroadaptations.

Escalation of cocaine intake and incubation of cocaine seeking are correlated with dissociable neuronal processes in different accumbens subregions.

Background: Cocaine addiction is characterized by a progressive increase in drug intake and a persistent craving for the drug during prolonged abstinence. Whether these two prominent features of cocaine addiction are related to each other and are mediated by similar or different neuronal processes is currently unknown.

Methods: Rats were first allowed to self-administer cocaine under long-access (6-hour) conditions to induce escalation of cocaine intake.

fMRI response in the medial prefrontal cortex predicts cocaine but not sucrose self-administration history.

Repeated cocaine exposure induces long-lasting neuroadaptations that alter subsequent responsiveness to the drug. However, systems-level investigation of these neuroplastic consequences is limited. We employed a rodent model of drug addiction to investigate neuroadaptations associated with prolonged forced abstinence after long-term cocaine self-administration (SA).

Acute effects of nicotine amplify accumbal neural responses during nicotine-taking behavior and nicotine-paired environmental cues.

Nicotine self-administration (SA) is maintained by several variables, including the reinforcing properties of nicotine-paired cues and the nicotine-induced amplification of those cue properties. The nucleus accumbens (NAc) is implicated in mediating the influence of these variables, though the underlying neurophysiological mechanisms are not yet understood. In the present study, Long-Evans rats were trained to self-administer nicotine.

Varenicline effects on cocaine self administration and reinstatement behavior.

This study tested the effects of the nicotine addiction treatment varenicline on cocaine self administration (SA) and reinstatement. In one SA experiment, rats were trained to self-administer cocaine (0.75 mg/kg/infusion).

Progressive and lasting amplification of accumbal nicotine-seeking neural signals.

Although neuroadaptations in the nucleus accumbens (NAc) are thought to contribute to nicotine addiction, little is known about the chronic effects of nicotine on NAc neuronal activity. In the present experiment, rats were exposed to a 23 d period of nicotine self-administration (SA), a 30 d abstinence period, and a 7 d period of reexposure to SA. Chronic electrophysiological procedures were used to record the activity of individual NAc neurons on the 3rd and 23rd days of initial SA and on the 1st, 3rd, and 7th days of reexposure.

Effects of acute amphetamine exposure on two kinds of Pavlovian approach behavior.

Two kinds of Pavlovian conditioned approach behavior are possible: approach of the CS (sign-tracking) and approach of the US (goal-tracking). We hypothesized that administration of AMP would increase sign-tracking and decrease goal-tracking. However, increasing doses of AMP (up to 2.

Orbitofrontal and insular cortex: neural responses to cocaine-associated cues and cocaine self-administration.

Based on neuro-imaging studies in cocaine-addicted humans, it is hypothesized that increases in neural activity within several regions of the prefrontal cortex contribute to cue-induced cocaine seeking and cocaine-induced compulsive drug self-administration. However, electrophysiological tests of these hypotheses are lacking. In the present study, animals were trained to self-administer cocaine (0.

Amphetamine exposure enhances accumbal responses to reward-predictive stimuli in a pavlovian conditioned approach task.

Acute and repeated exposure to psychostimulants such as amphetamine enhances the effects of pavlovian conditioned stimuli on conditioned behavior. It is hypothesized that amphetamine facilitates conditioned stimulus (CS) effects by selectively enhancing accumbal neuronal responses to stimuli. To test this hypothesis, rats were trained to discriminate between two pavlovian stimuli.

Background firing rates of orbitofrontal neurons reflect specific characteristics of operant sessions and modulate phasic responses to reward-associated cues and behavior.

The orbitofrontal cortex plays an important role in the ability of animals to adjust their behavior in response to behavioral outcomes. Multiple studies have demonstrated that responses of orbitofrontal neurons during operant sessions reflect the outcome of particular behaviors. These studies have focused on rapid neural responses to short-duration events such as instrumental behavior and reward-associated discrete cues.

Selective strengthening of conditioned behaviors that occur during periods of amphetamine exposure.

Exposure to psychomotor stimulants, during conditioning sessions, can lead to a persistent increase in the strength of conditioned behaviors and the effects of conditioned stimuli, which can be detected in subsequent drug-free periods. It is possible that the effects are selective for the behaviors and stimuli conditioned during drug exposure. The present study was designed to test this prediction.

Accumbal neurons that are activated during cocaine self-administration are spared from inhibitory effects of repeated cocaine self-administration.

Hypoactivity of the accumbens is induced by repeated cocaine exposure and is hypothesized to play a role in cocaine addiction. However, it is difficult to understand how a general hypoactivity of the accumbens, which facilitates multiple types of motivated behaviors, could contribute to the selective increase in drug-directed behavior that defines addiction. Electrophysiological recordings, made during sessions in which rats self-administer cocaine, show that most accumbal neurons that encode events related to drug-directed behavior achieve and maintain higher firing rates during the period of cocaine exposure (Task-Activated neurons) than do other accumbal neurons (Task-Non-Activated neurons).

Session-long modulations of accumbal firing during sucrose-reinforced operant behavior.

The nucleus accumbens is involved in the selection and expression of motivated behaviors. Attempts to understand how activity of single neurons in the accumbens relates to behavior have largely concentrated on brief modulations in accumbal firing that occur in the seconds around events during operant sessions. However, a small number of studies have reported modulations that last the entire duration of a behavioral session.

Firing patterns of accumbal neurons during a pavlovian-conditioned approach task.

The nucleus accumbens (NAc) is necessary for the expression of Pavlovian-conditioned approach behavior but not for the expression of instrumental behavior conditioned in sessions that set a low response requirement. Although numerous studies have characterized firing patterns of NAc neurons in relation to instrumental behavior, very little is known about how NAc neurons encode information in Pavlovian tasks. In the present study, recordings of accumbal firing patterns were made during sessions in which rats performed a Pavlovian-conditioned approach task.

Accumbal neural responses during the initiation and maintenance of intravenous cocaine self-administration.

During a chronic extracellular recording session, animals with a history of cocaine self-administration were allowed to initiate drug seeking under drug-free conditions. Later, in the same recording session, animals engaged in intravenous cocaine self-administration. During the drug-free period, 31% of 70 accumbal neurons showed a significant increase in average firing rate in association with either or both the exposure to cues that signaled the onset of cocaine availability and the subsequent onset of drug-seeking behavior.

Differential changes in signal and background firing of accumbal neurons during cocaine self-administration.

Learning theories of drug addiction propose that the disorder is, at least in part, attributable to drug effects on accumbal mechanisms that are normally involved in reward-related learning. The neurophysiological mechanisms that might transduce such a drug effect on accumbal mechanisms have yet to be identified. Previous studies showed that a population of accumbal neurons exhibit phasic excitatory responses time locked to cocaine-reinforced lever presses during intravenous cocaine self-administration sessions (neurons referred to as lever-press neurons).