1,721,057 research outputs found
Addiction research and theory: a commentary on the surgeon general's report on alcohol, drugs, and health
Full text linkThe Office of the Surgeon General recently produced its first Report on the consequences of alcohol and drug abuse on health, making several very laudable policy recommendations. The Report also emphasizes the importance of adequate funding for biomedical research, which is good news for both researchers and patients. However, the Report is marred by a biased viewpoint on the psychology and neurobiology of drug addiction. We highlight here four controversial issues that were depicted as facts in the Report, thereby potentially misleading non-expert readers about the current state-of-the-art understanding of the psychology and neurobiology of drug addiction. It will be important to recognize a fuller range of scientific viewpoints in addiction neuroscience to avoid amplifying this bias in the coming years
Functional heterogeneity of striatopallidal subregions.
No full textDisruption of the striatopallidal system in humans can produce involuntary hyperkinetic movements, an impairment of action sequencing, and emotional changes such as major depression. Large lesions of the striatopallidal system in the rat produce a sensory-triggered hyperkinetic forelimb treading, an impairment of the serial order of grooming sequences and an enhancement of aversion to normally palatable tastes. The goals of this dissertation were to discover whether these changes are caused by damage to different striatopallidal subregions. A novel lesion mapping technique called the modified fractionator technique was invented to map the crucial site for each syndrome. The crucial site for hyperkinetic treading was within the ventromedial corner of the globus pallidus. Damage exceeding 60% neuron loss bilaterally within this 0.8 x 1.0 x 1.0mm subterritory produced this syndrome. Haloperidol, a dopamine receptor blocker, suppresses human hyperkinetic movements and was also found to reduce the hyperkinetic forelimb treading in the rat. The crucial site for disruption of the serial structure of grooming sequences was restricted to a dorsolateral portion of the neostriatum. Damage exceeding 72% neuron loss bilaterally within this 1.3 x 1.0 x 1.0mm subterritory produced this sequential impairment. The ability to initiate or execute grooming actions such as forelimb strokes or body licks was not impaired in rats that had sequencing deficits. Only the ability to sequence a set of grooming actions into a specific serial order was impaired. The crucial site for the enhancement of taste aversion was restricted to the ventromedial ventral pallidum/substantia innominata. Damage exceeding 70% neuron loss bilaterally within this 1.0 x 0.5 x 1.0mm subterritory produced this enhanced taste aversion. Bilateral lesions centered within the lateral hypothalamus itself did not produce a similar enhancement of taste aversion even though they produced aphagia. In conclusion, specific striatopallidal syndromes result from damage localized to different sites. This result has implications for the understanding of the functional heterogeneity of the striatopallidal system both for normal function and for motor, cognitive and emotional dysfunction in human striatopallidal disease.PhDPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/103738/1/9409668.pdfDescription of 9409668.pdf : Restricted to UM users only
Reward and motivation in the ventral pallidum: Chemical, physiological, and anatomical mechanisms.
No full textA fundamental question in the neuroscience of reward is how the brain takes sensory input and adds hedonic or incentive value to it. My dissertation focuses on neural mechanisms for 'liking' and 'wanting' in two limbic brain structures, the ventral pallidum (VP) and nucleus accumbens (NAc). The VP is a chief output site for the NAc, and together they form a circuit linking limbic areas to cognitive and motor systems. My goal is to identify neurochemical, neuroanatomical and electrophysiological mechanisms for 'liking' and 'wanting' in VP and NAc, and in circuit features of how the two structures are functionally connected together. In my first project, I use a microinjection and immediate early gene (Fos) mapping technique to identify a hedonic hotspot in the caudal VP where mu opioids can function to elevate 'liking' for taste rewards and 'wanting' for food. The NAc has also been discovered recently to contain its own opioid hotspot for 'liking' and 'wanting'. Thus, in my second project, I seek to characterize if, and how, these two hotspots interact. I first observe that opioid stimulation in one hotspot recruits neurobiological Fos activity in the other, suggesting they communicate bidirectionally. To explore functional connections I next use simultaneous NAc and VP microinjections, and find that both hotpots work together as obligatory stages of a single circuit, rather than independently, to elevate reward 'liking'. However, I discover that the NAc can elevate eating independently of the VP, revealing overlapping but distinct circuitry for 'liking' versus 'wanting'. My third project asks the question of how neuronal activity within a hotspot might encode increases in 'liking' or 'wanting'. Using simultaneous NAc microinjection and VP electrophysiological recording, I find that VP neurons can encode elevations in 'liking' and 'wanting' that arise from opioid or dopamine stimulation in the NAc. These results reveal a causal role for the VP in increasing reward 'liking' and 'wanting', reveal a code for those functions within VP, and reveal how the VP functions within a larger reward circuit. The VP may therefore be an important target for future research on normal and pathological goal-directed behavior.PhDBiological SciencesNeurosciencesPsychobiologyPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/126824/2/3276296.pd
Contrasting roles of mesostriatal dopamine and opioid systems in food 'wanting' and 'liking'.
No full textWhat role do brain dopamine and opioid systems play in the mediation of reward? Do these neurotransmitter systems mediate pleasure? Are reward and pleasure identical? What neural substrates mediate the 'liking' component of reward? The 'taste reactivity paradigm' of affective reactions to tastes was used to investigate the role of dopamine and opioid agents in taste pleasure and to identify neural substrates involved in its regulation. The taste reactivity technique is the only paradigm that allows assessment of the 'liking' for a taste incentive independently from 'wanting' components of reward, and thus the most direct measure available for the study of hedonic regulation. Results indicate that while dopamine and opioid systems are implicated in the mediation of reward, only the brain opioid systems are involved in the regulation of hedonic processes. Brain dopaminergic systems are not. In addition, the boundaries of the specific subregion within the nucleus accumbens (a forebrain structure related to motivation and reward) that mediates opioid-induced feeding were defined. A c-fos based technique was used to identify plumes of neuronal activation triggered by intra-accumbens microinjections of morphine (0.5 g) that elicit feeding. Based on the determined size and shape of morphine-induced fos plumes, a mapping procedure identified the extent and boundary of the accumbens 'opioid-eating' site. The site was found to be contained primarily within a medial caudal subregion of the nucleus accumbens shell, and did not substantially penetrate the accumbens core. However, portions of several other structures, immediately medial and adjacent to the shell, appeared to be included in the functional site (such as rostral ventral pallidum and vertical limb of the diagonal band). Finally, it was shown that hedonic taste reactivity patterns were also enhanced by microinjections of morphine into the accumbens 'opioid eating site'. This suggests that accumbens opioid-mediated increases in food intake involve an enhancement in the impact of taste pleasure. Increases in both 'wanting' and 'liking' for food after accumbens administration of opioid agonists thus appear to be mediated by opioid receptors localized primarily in the medial and caudal shell of the nucleus accumbens.PhDPsychobiologyPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/131507/2/9909964.pd
Accumbens shell organization of positive and negative motivational states: GABA and glutamate rostrocaudal gradients.
No full textHow mesolimbic systems mediate the positive versus negative valence of motivational states has been an important topic in affective neuroscience. The present thesis examined neurobiological mechanisms controlling appetitive versus defensive motivation within the nucleus accumbens shell. Animals received microinjections of GABA agonist and glutamate antagonists throughout accumbens shell and were behaviorally tested for appetitive eating, defensive treading, distress vocalization, bites and related fear behavior, conditioning of place preference/avoidance, and hedonic/aversive reactions to tastes. Our findings demonstrated that GABA and glutamate neurotransmission organizes appetitive and defensive behavior into separate streams of information along motivational positive-to-negative rostrocaudal gradients in medial accumbens shell. Rostral shell microinjections elicited appetitive behaviors such as eating, conditioned place preferences, and increased hedonic reactions to sweet tastes. Conversely, caudal shell injections produced defensive behaviors such as defensive treading, distress vocalizations, bites and related fear behavior, conditioned negative place avoidances, and increased aversive reactions to tastes. These results agree with suggestions that behavioral function within the accumbens is mediated by separable populations, or ensembles, of neurons within nucleus accumbens, organized by glutamate transmission. Furthermore, rostral shell appetitive versus caudal shell defensive ensembles were dynamically reorganized by inputs relaying information about environmental valence, value, and sensory intensity. Caudal shell defensive ensembles normally recruited by blockade of glutaminergic inputs in standard lab conditions were reduced and ineffective in safe and familiar environments. Defensive ensembles expanded to include both rostral and caudal shell in aversive and threatening contexts. Conversely, rostral shell appetitive ensembles mediated multiple appetitive behaviors in safe and familiar contexts but only a single appetitive behavior in more aversive environments. This suggests the involvement of a plastic component of motivation, such as motivational salience, that can be influenced by both rostrocaudal location of shell microinjection and by modulation of inputs to the shell that reflect factors such as environmental valence. Thus the experiments in this thesis suggest that GABA and glutamate neurotransmission in nucleus accumbens mediates both positive and negative motivational states in separate, but overlapping, neuronal ensembles within in medial shell that can be appropriately modulated by environmental contexts to allow the animal to adaptively respond to environmental challenges.PhDPsychobiologyPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/123463/2/3079518.pd
Neostriatal Dopamine Modulates Motivation: Incentive Salience Generation in the Neostriatum
Full text linkNeurosciencehttp://deepblue.lib.umich.edu/bitstream/2027.42/85246/1/dbushart.pd
Coding of rewarded tasks by ventral pallidum neurons: Learning, hedonics, and incentive value.
No full textThe ventral pallidum (VP) is a brain structure essential for reward learning and motivation. However, little is known about how VP neurons actually process reward information. In these studies, neural activity in the VP was recorded in freely moving rats as they learned a Pavlovian task in which specific stimuli predicted a reward. The first study demonstrated that VP neuronal firing encodes learning and reward by increasing the number of neurons that respond to reward-predicting stimuli, and by varying the speed at these neurons fire. In subsequent studies, I asked whether VP firing to stimuli during the task reflect purely predictive information or also motivational reward (incentive salience) properties of the stimuli. I induced physiological shifts in rats' motivational state after learning by sensitizing rats to amphetamine (which enhances incentive motivation for rewards) or depleting rats of sodium (which selectively enhances salt taste reward). Changes in VP firing following these motivational shifts allowed us to compare directly prediction models versus motivational incentive salience models. After amphetamine sensitization, VP neurons immediately increased their response to the predictive stimulus associated with a relevant reward, indicating coding of motivational incentive salience. Our novel computational Profile Analysis technique showed a shift in VP firing toward the stimulus with highest motivational incentive salience. These shifts in coding occurred without new learning about the predictive tones, again indicating motivational value influenced by physiological states. My last experiments showed that VP firing codes hedonic impact of rewards themselves, in addition to incentive motivational value of learned stimuli that predict reward. After physiological sodium depletion caused the taste of concentrated triple-seawater salt, which normally is 'disliked', to become strongly 'liked', VP neurons increased firing to the taste in a manner that coded hedonic reward value. My results demonstrate that VP neurons code the motivational value of cues and rewards, tracking that value through shifts in homeostasis, and extracting information about learned stimuli that reflects the current motivational value of the rewards they predict. These data emphasize the ability of VP neurons to multiplex information about reward prediction and motivation by integrating learned predictive associations and dynamic physiological states. My studies reveal important roles for VP neurons in coding normal reward learning and motivation, and suggest that VP dysfunction may be implicated in human motivational disorders including drug addiction and eating disorders.PhDBiological SciencesNeurosciencesPhysiological psychologyPsychobiologyPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/125237/2/3186772.pd
The Associative Representation of Fear Memories Mediated by the Amygdala.
Full text linkThis dissertation investigates how memories for emotional events are represented within the brain. The amygdala is a region of the brain that has been identified as playing a major role in emotional memory. The amygdala contains two subregions, the basolateral complex and the central nucleus, which have been found to be important in the acquisition and expression of emotional memories, respectively. For example, damage to either brain area in rats or humans prevents the acquisition of Pavlovian fear conditioning, a form of emotional learning in which neutral stimuli that do not provoke fear come to do some after being paired with an aversive event.
However, rats with damage to the basolateral amygdala can acquire fear if given sufficient experience (e.g., many conditioning trials) and it appears that the central nucleus acquires fear memories under these conditions. These findings suggest that either the nature of the memories acquired during limited or extensive training are different, which therefore recruits different brain areas, or the amygdala subregions serve similar roles in fear learning. To address this, the author first examined whether the nature of fear memories formed after limited and extensive training are in fact different. Previous work has suggested that early in conditioning the ability of a conditioned stimulus to produce learned responses is based on retrieving a memory of the aversive outcome, but that after extensive training the conditioned stimulus directly retrieves the learned response. The author therefore manipulated the animals’ representation of the aversive outcome after fear conditioning to assess whether fear memories depend on an expectation of an aversive event. Even after extensive training fear memories were dependent on the expectation of an aversive event, suggesting that the nature of learned fear associations does not change as a function of training.
Next, the author investigated whether the nature of learned fear associations mediated by the basolateral complex and central nucleus are similar. Using either permanent or temporary lesions of the amygdala, it was found that both basolateral and central nucleus-dependent memories are affected by post-conditioning changes in the value of the aversive outcome, suggesting that they depend on thePhDPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/62330/1/rabinak_1.pd
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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