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Laura L Peoples

Publications and source records attributed to Laura L Peoples.

7 recordsLinked to original sources
PubMed2006

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. Animals were trained to discriminate two sets of stimuli. For each set, lever pressing during the presentation of one stimulus (S+) was reinforced and responding during the presentation of the other stimulus (S-) had no programmed consequences. Following an initial acquisition phase, training with one set of stimuli continued during sessions of amphetamine exposure, whereas training with the second set continued during saline exposure (20 intermixed sessions). The findings of subsequent drug-free choice tests showed that the drug history selectively enhanced the propensity of animals to engage in the drug-assigned behavior relative to the saline-assigned behavior. This change in behavior was evident in S+, but not S- trials and was potentially mediated by an acute effect of amphetamine on stimulus conditioning. The findings provide novel evidence that the facilitative effects of coincident conditioning and acute psychomotor stimulant exposure can be selective for the stimuli and behaviors conditioned during the drug exposure. These findings are relevant to hypotheses regarding the etiology of drug addiction.

Amphetamine↗
PubMed2006

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). We have hypothesized that this difference in activity makes the neurons that facilitate drug-directed behavior less susceptible than other neurons to the chronic inhibitory effects of cocaine. A sparing of neurons that facilitate drug-directed behavior from chronic hypoactivity might lead to a relative increase in the transmission of neuronal signals that facilitate drug-directed behavior through accumbal circuits and thereby contribute to changes in behavior that characterize addiction (ie differential inhibition hypothesis). A prediction of the hypothesis is that neurons that are activated in relation to task events during cocaine self-administration sessions will show less of a decrease in firing across repeated self-administration sessions than will other neurons. To test this prediction, rats were exposed to 30 daily (6 h/day) cocaine self-administration sessions. Chronic extracellular recordings of single accumbal neurons were made during the second to third session and the 30th session. Between-session comparisons showed that decreases in firing were exhibited by Task-Non-Activated, but not by Task-Activated, neurons. During the day 30 session, the magnitude of the difference in firing rate between the two groups of neurons was positively related to the propensity of animals to seek and take cocaine. The findings of the present study are consistent with a basic prediction of the differential inhibition hypothesis and may be relevant to understanding cocaine addiction.

Action Potentials↗
PubMed2006

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. Most of the recorded neurons (74/83, 89%) exhibited significant responses during the conditioned stimulus (CS) presentation and/or the reward exposure. The reward responses were prevalent, predominantly inhibitory, and comparable to reward responses observed in various types of behavioral paradigms, including instrumental tasks. The CS responses could be segregated into multiple subtypes on the basis of directionality, onset latency, and duration. Several characteristics of the CS firing patterns were unique relative to cue responses observed previously during alternative types of conditioning sessions. It is possible that the novel firing patterns correspond to the differential contributions of the accumbens to Pavlovian-conditioned approach behavior and instrumentally conditioned behavior. Regardless, the novel patterns of firing add to existing evidence that characterization of accumbal firing patterns in Pavlovian tasks may provide additional information about the neurophysiological mechanisms that mediate accumbal contributions to behavior.

Animals↗
PubMed2006

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. In all of these reports, the operant session was a drug self-administration session. The present study tested the hypothesis that session-long modulations, like phasic firing patterns, are components of normal accumbal activity during periods of instrumental behavior. Eight rats were chronically implanted (unilaterally) with microwire arrays in the nucleus accumbens, and trained to lever press on a Fixed-Ratio 1 schedule of sucrose reinforcement. Activity of 51 single units was recorded, and both session-long increases (n = 14) and session-long decreases (n = 13) were observed. These findings show that session-long modulations are a normal component of the response of accumbal neurons during periods of operant behavior. Moreover, although session-long modulations during cocaine self-administration sessions might reflect pharmacological actions, aspects of the modulations might additionally or alternatively correspond to afferent-driven responses. Further characterization of the firing patterns may elucidate novel mechanisms that mediate accumbal contributions to behavior.

Animals↗
PubMed2003

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. The neurons that showed an average excitatory response during the drug-free period were the only group of neurons that showed an average excitatory phasic response to cocaine-reinforced lever presses during the drug self-administration session. A majority of the neurons that were activated during the drug-free period, like the majority of other neurons, showed decreases in average firing in response to self-administered cocaine. However, the neurons that were activated during the drug-free period maintained a higher rate of firing throughout the self-administration session than did other accumbal neurons. The data of the present study are consistent with the conclusion that accumbal neurons contribute to, or otherwise process, initiation of drug seeking under drug-free conditions and that they do so via primarily excitatory responses. Furthermore, there is continuity between the drug-free and -exposed conditions in neural responses associated with drug seeking. Finally, the data have potential implications for understanding mechanisms that transduce accumbal-mediated drug effects that contribute to drug addiction.

Action Potentials↗
PubMed2003

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). Most of the same neurons, like the majority of accumbal neurons, also show a decrease in average firing rate during the drug self-administration session. Evidence indicates that the phasic firing patterns transmit information related to drug-reward-related events. On the other hand, the decreases in average firing reflect a primary pharmacological effect of self-administered cocaine. In the present study, we tested the hypothesis that the phasic firing associated with drug seeking (i.e., signal) is less sensitive than other accumbal firing (i.e., background) to the inhibitory effect of cocaine. During intravenous cocaine self-administration sessions, 45 of 68 neurons showed a decrease in average firing during the self-administration session relative to a predrug baseline period. Fourteen neurons showed both an inhibition in average firing and an excitatory phasic response. For these 14 neurons, signal either remained equal to the average predrug firing rate or exceeded the predrug firing rate during the self-administration session. For the same neurons, background firing generally fell below average predrug firing. The differential changes in signal and background were associated with an increase in the ratio of signal-to-background for the individual neurons. Moreover, the relatively unique resistance of signal to inhibition was associated with an increase in the ratio of signal firing of all lever-press neurons relative to the background firing of all recorded neurons. This type of differential inhibition in signal and background firing might be expected to increase the relative influence of the drug-reward-related signals on accumbal-related neural circuits and differentially influence susceptibility of drug- and non-drug-reward-related synaptic and neural responses to neuroplasticity. It thus represents a mechanism by which inhibitory effects of self-administered drug might amplify the accumbal contribution to behavior and learning and potentially contribute to drug addiction.

Action Potentials↗