Universiẗat, Diss., 2003--Stuttgart.

The mesoaccumbens dopamine system has been implicated in many basic psychological processes (e.g. "wanting" and "liking") and illnesses (e.g. addiction, depression, schizophrenia). However, the precise computational functions of nucleus accumbens and dopamine neurons within the system remain unknown. In this thesis, we test some of the current hypotheses regarding the function of this system using a behavioural neurophysiology approach in the rat. The first question we wanted to answer was whether nucleus accumbens neurons process reward-predictive stimuli (e.g. conditioned reinforcers) and reward delivery differently, since previous studies report equivocal findings. To do so, we trained thirsty rats to bar-press on a second-order schedule of saccharin reinforcement, within which the temporal pattern of rats' bar-pressing was reinforced by presentations of a conditioned reinforcer and primary reinforcer (reward). We found that nucleus accumbens neurons typically responded to these conditioned and primary reinforcers with opposite sign, which suggests they were processed differently. We were not sure whether responses to conditioned reinforcers encoded reward-prediction or facilitated a behavioural switch in the rat's behaviour. Indeed, since studies using a variety of experimental techniques have implicated the mesoaccumbens dopamine system in both reward prediction and behavioural switching, we sought to test whether neurons in the nucleus accumbens and dopamine-rich areas of the midbrain respond to outcome-associated stimuli to predict reward or switch behaviour. We found both sets of neurons predominantly did the former. Finally, to understand more about reward consummatory responses from both sets of neurons, we developed a rat behavioural task providing measures of reward "wanting" and "liking". In conclusion, on the basis of our data, the most parsimonious explanation for the function of the mesoaccumbens dopamine system is that it acts to modulate goal-seeking behaviour. Further research is required to identify the function of the interactions between nucleus accumbens and dopamine neurons during goal-seeking and goal consumption.

Psychological stressors such as social stress and bullying are prevalent in today’s society. Disorders such as PTSD, depression and social anxiety disorder can be either caused or exacerbated by social stress and treatment options are not always effective in providing relief for these disorders. Our laboratory studies a form of social stress termed conditioned defeat, whereby a defeated Syrian hamster no longer displays species-typical territorial aggression but instead is submissive and defensive toward an intruder in its own cage. We hypothesized that the nucleus accumbens is a necessary component of the circuit mediating the acquisition and expression of conditioned defeat and that dopamine is necessary within the nucleus accumbens for inducing memory processes as well as expression of behavioral responses to stressful situations. We also hypothesized that defeat activates dopaminergic and/or nondopaminergic neurons in the ventral tegmental area (VTA) and that dopamine released by neurons projecting from the VTA to the nucleus accumbens and basolateral amygdala (BLA) increases neuronal activation of these structures during defeat. We found that dopamine, but not GABA, modulates memory of social defeat within the nucleus accumbens. However, GABA does affect the expression of behavioral responses to social defeat. Defeat also increased Fos activation of non-dopaminergic neurons, but it did not increase activation of dopaminergic neurons. Baclofen infusion into the VTA prior to defeat, which was hypothesized to specifically inhibit dopaminergic neurons, did not affect Fos activation within the nucleus accumbens and the basolateral amygdala. These experiments determined that dopamine does modulate memory of social defeat within the nucleus accumbens, but it is currently unclear what the source of this dopamine is. Future experiments are planned to determine this source of dopamine that could be a target of treatment for disorders that are caused or exacerbated by social stress.

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

Previous research has suggested that lobeline, a plant alkaloid derived from Lobelia inflate, has potential to be an efficacious pharmacotherapy for the treatment of methamphetamine dependence. In addition to attenuating methamphetamineinduced dopaminergic alterations in vitro, lobeline has been shown to decrease the primary rewarding effects and discriminative stimulus properties of methamphetamine in rats. It is of clinical interest to assess the utility of lobeline to decrease methamphetamine conditioned cues as these cues have been shown to significantly contribute to relapse. The current studies assessed the ability of lobeline to block the acquisition and expression of methamphetamine-induced conditioned place preference in rats. Lobeline blocked the acquisition of methamphetamine-induced conditioned place preference when a low dose of methamphetamine was used during conditioning. However, this blockade was surmounted with higher doses of methamphetamine. Furthermore, the expression of methamphetamine-induced conditioned place preference is attenuated following repeated administration, indicating that lobeline not only blocks the primary reinforcing effects of methamphetamine, but it also blocks the environmental cues that become associated with drug administration. These results provide further evidence that lobeline may be an efficacious treatment for methamphetamine dependence. The rewarding properties of psychostimulants are thought to be mediated, at least in part, by the nucleus accumbens shell. The effects of lobeline on methamphetamine-induced alterations in this dopaminergic region were assessed using microdialysis in rats. Acute lobeline did not have an effect on the methamphetamine-induced increases in dopamine, indicating that repeated lobeline administration may be more efficacious. Interestingly, lobeline potentiated the methamphetamine-induced decrease of the dopamine metabolite, DOPAC. These results suggest that acute lobeline may function to redistribute vesicular dopamine pools within the terminal bouton.

Thesis advisor: John P. Christianson / In social species, animals must detect, evaluate and respond to the states of other individuals in their group. A constellation of gestures, vocalizations, and chemosignals enable animals to convey affect and arousal to others in nuanced, multisensory ways. Observers integrate such social information with environmental cues and internal physiology to general social behavioral responses via a process called social decision-making. The mechanisms and anatomical correlates of social decision-making, particularly those that allow behavioral responses to others’ emotional states, are not fully known. Therefore, the objective of this dissertation is to broaden the anatomical understanding of social decision-making by investigating the role of the insular cortex in social behaviors that depend upon others’ emotional state. Using a novel behavioral paradigm, I present causal evidence that implicates the insular cortex and its projections to the nucleus accumbens in social affective behavior. These findings are consistent with evidence from the literature that suggests insular cortex is positioned to convey sensory cues to social brain structures to produce flexible and appropriate behavioral responses to social affective cues. / Thesis (PhD) — Boston College, 2019. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Psychology.

Thesis advisor: Jon C. Horvitz / Previous research has yielded conflicting results regarding the involvement of mesolimbic dopamine in Pavlovian and operant tasks. While there is abundant evidence that an operant lever press requires intact dopamine (DA) D1 transmission in the nucleus accumbens (ACB) and in the basolateral amygdala (BLA), there is conflicting evidence regarding the specific brain sites at which DA mediates a Pavlovian approach response. The present study was designed to compare the effects of ACB and BLA D1 receptor-blockade on an operant and Pavlovian task, while minimizing differences in behavioral response topography. Animals were trained on either a Pavlovian cued approach task or an operant cued nosepoke task. In the Pavlovian approach task, a tone signaled a pellet delivery to which animals responded with a head entry into a food compartment. In the operant nosepoke task, animals were trained to emit a nosepoke in response to the same tone, in order to trigger a pellet delivery. Bilateral microinfusions of the D1 antagonist SCH 23390 (0, 1 or 2 microgram/side) into either the ACB or the BLA produced a dose-dependent disruption of the operant nosepoke. In contrast, the Pavlovian cued approach response was unaffected by D1 antagonist microinfusions into either the ACB or the BLA. In addition, infusion of SCH 23390 into either site suppressed general locomotion. The results suggest a dissociation of the anatomical substrates mediating an operant nosepoke and a Pavlovian approach, despite similar response topographies. These findings are consistent with the notion that D1 activity at the ACB and BLA plays a role in the expression of operant responses, but not in the expression of Pavlovian approach responses. / Thesis (PhD) — Boston College, 2010. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Psychology.

Thesis advisor: Michael Numan / Postpartum female rats immediately respond to biological or foster offspring with the display of maternal behavior. In contrast, females that are hysterectomized and ovariectomized on day 15 of pregnancy (15HO) and presented with pups 48 hours later show maternal behavior after 2-3 days of pup exposure. The natural onset of maternal behavior in postpartum females is mediated, in part, by the rise in estradiol just prior to birth. When 15HO rats are administered estradiol benzoate (EB) at the time of HO surgery, 48 hours prior to pup presentation, they show an almost immediate onset of maternal behavior. Presumably, EB administration functions to prime neural circuits which regulate maternal behavior such that these circuits respond to pup presentation with increased maternal responsiveness. Two important neural regions which have been shown to interact in order to promote responsiveness toward infant stimuli are the medial preoptic area (MPOA) and the nucleus accumbens (NA). The following series of studies were undertaken to examine how dopamine (DA) activity within these two important neural sites substitutes for the facilitatory effects of chronic (48 hours) EB stimulation of maternal behavior in 15HO rats. Study 1 investigates whether, in the absence of EB treatment, microinjection of dopamine receptor agonists into either NA or MPOA at the time of pup presentation stimulate maternal behavior in 15HO rats. Study 2 examines the underlying mechanism by which DA receptor stimulation of NA promotes the onset of maternal behavior in 15HO rats. Finally, Study 3 examines the relationship between DA receptor stimulation and estradiol stimulation in the facilitation of maternal responsiveness in 15HO rats. / Thesis (PhD) — Boston College, 2009. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Psychology.

Frågan om människans drivkrafter och vad som ligger bakom våra handlingar har en lång historia och ju mer man har försökt att förklara och definiera begreppet motivation desto mer komplext tycks det ha blivit. Den här uppsatsens syfte är att ge en förståelse till komplexiteten kring problematiken om begreppet motivation. Detta görs genom att belysa dess djupa rötter i filosofins och psykologins värld samt lyfta fram några av motivationsteorierna ur den omfattande breda litteraturen som skrivits om ämnet. Vidare genom att belysa vad den moderna neurovetenskapliga forskningen har tillfört i studierna om motivation. Resultatet visar på att de gamla klassiska motivationsteorierna än idag influerar på ämnet. Självbestämmandeteorin (SDT) visar på att det finns olika typer av motivation och att vi föds med tre psykologiska behov som ligger till grund för en individs intrinsiska och extrinsiska motivation. Den affektiva neurovetenskapen visar på att det finns en ömsesidig interaktion mellan kognition, affektion och beteende som baseras på djupa evolutionära emotionella rötter djupt in i det limbiska systemet. Bevis finns för att nucleus accumbens (NAc) spelar en viktig roll i val av handlingsalternativ som underlättar och effektiviserar målorienterat beteende samt har både exciterande och inhiberande funktion på beteende.