Browsing by Subject "Dopamine--Physiological effect"
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Item Dopamine and ethanol induced trafficking of viral mediated eGFP tagged dopamine D1 receptors in parasagittal explants(2005) Diaz, Laurea Marie; Morrisett, Richard A.The mesolimbic pathway has been implicated in the rewarding effects of drugs of abuse, and an important component of this pathway is the D1 dopamine receptor (D1DR). D1DRs desensitize upon agonist stimulation by several mechanisms, including a process involving receptor clustering and internalization. This process removes postsynaptic D1DRs and may be a neuroadaptive mechanism associated with addiction to drugs of abuse, including ethanol. We measured localization of D1DRs in viable nucleus accumbens (NAcc) neurons from parasagittal explants. A sindbis RNA virus was used to mediate the expression of D1DRs containing an enhanced green fluorescent protein (eGFP) tag in these explants. The effects of dopamine and ethanol on D1DR localization were measured by changes in fluorescence intensity using two-photon laser scanning microscopy. Two-dimensional images from z-stacks of virally infected neurons displayed stable and homogenous fluorescence throughout the neuronal soma and processes. Dopamine (100 uM, 30 min) significantly enhanced the greatest increase of maximum fluorescence intensity in distinct regions of interest (ROIs) by approximately 40% compared to control neurons in the absence of dopamine. Ethanol pretreatment significantly enhanced dopamine-induced clustering. Neurons exposed to dopamine (50 uM, 30 min) displayed receptor clustering only when pretreated with ethanol. Ethanol (50 and 100 mM, 30 min.) pretreatment followed by dopamine (50 uM, 30 min.) enhanced the greatest increase of maximum fluorescence intensity by 44±3 and 108±9%, respectively, while dopamine (50 uM, 30 min) in the absence of ethanol pretreatment showed no clustering with peak increases in maximum fluorescence intensity of only 3±2%. Ethanol (50 and 100 mM, 60 min) alone enhance the greatest increase of maximum fluorescence intensity by about 60% for both concentrations. Receptor clustering induced by dopamine, ethanol pretreatment of dopamine, or ethanol alone was partially blocked by the D1DR antagonist SCH 23390 (20 uM). These findings show that both dopamine and ethanol alter D1DR localization in NAcc neurons and suggest that a physical restructuring of D1DRs in this region may be involved in neuroadaptive mechanisms of ethanol actionItem Dopamine D1-like receptor-mediated regulation of NMDA receptor sensitivity to ethanol in the nucleus accumbens(2005) Zhang, Tao; Morrisett, Richard A.Item The effect of ethanol consumption on dopamine and ethanol concentrations in the nucleus accumbens during the development of reinforcement and the involvement of the k-Opioid receptor in the modulation of dopamine activity during ethanol self-administration(2005) Doyon, William Maurice; Gonzales, Rueben A.Item Genetic and experiential effects on dopaminergic systems(2002) Woolley, Sarah Cushing; Crews, David.; Bronson, F. H.Successful reproduction requires the coordination of relevant sensory inputs with motivational and motor systems primed by sex steroid hormones to produce an appropriate hierarchical sequence of movements. Both behavioral and neural phenotypes can be altered by social interactions that, in turn, can produce long term changes in cellular activity and signaling, neural circuitry, and sexual behavior. There is considerable variability in the type and direction of neural and behavioral change in response to social interactions, and the degree of plasticity may depend on intrinsic or genetic individual differences. Dopaminergic systems modulate the expression of social and sexual behaviors in a number of vertebrate species and intrinsic differences in dopaminergic systems may underlie intrinsic individual differences in the display of sexual behavior. Here, I present data on how social interactions, genotype, and steroid hormones can affect dopamine synthesis in limbic and midbrain nuclei. I investigated this in three model systems including knockout mice and two related species of whiptail lizard. The knockout mice have a targeted deletion of the progesterone receptor and display higher mount and intromission frequencies than wild-type males. Male whiptail lizards (Cnemidophorus inornatus) have natural variation in the display of courtship behaviors: some males are more sexually vigorous than others. Finally, individuals of the parthenogenetic species C. uniparens, which arose from two hybridization events involving the sexual species C. inornatus, display both maleand female-like sexual behaviors depending on reproductive state. In contrast, C. inornatus females only display receptive behavior, and this only during when preovulatory. In all three species, individuals that displayed greater levels of mounting behaviors had greater numbers of cells expressing tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, in the substantia nigra pars compacta. In addition, in male whiptail lizards and the related parthenogen, dopamine production in the dorsal hypothalamus was correlated with the propensity to display mounting behaviors. Dopamine can increase the display of mounting behavior in mice as well as in male and parthenogenetic whiptail lizards. My dissertation indicates that not only is dopamine sufficient to elicit mounting behavior, but differences in dopamine production may contribute to individual differences in behavioral phenotype.Item Involvement of dopamine in the nucleus accumbens and prefrontal cortex in cocaine-associative learning(2003) Ikegami, Aiko; Duvauchelle, Christine L.Stimuli formerly associated with cocaine-taking behavior are known to elicit physiological changes and craving in cocaine-dependent individuals. This is a result of learned associations between an environmental stimulus and the effects of cocaine, and is believed to be a major factor that leads to relapse in recovering cocaine addicts. A precise neural mechanism underlying how cocaine-paired stimuli produce craving and drug-taking behavior is currently unknown. Synaptic plasticity is known as a neural basis for associative learning. A modulatory role of a neurotransmitter, dopamine (DA), in synaptic plasticity has been implicated. Moreover, recent studies indicate that DA is particularly important during acquisition of associative learning, but less important as learning progresses. Yet, this notion has not been fully investigated using cocaine as a reinforcer. The nucleus accumbens (NAcc) and medial prefrontal cortex (mPFC) brain regions, are both largely implicated in drug addiction. Using an animal model of drug- taking behavior in conjunction with an in vivo microdialysis technique, the dissertation experiments determined the involvement of DA in during distinctive stages of cocaine associative learning. Results from the experiments showed that NAcc DA was responsive to cocaine-paired stimuli during early, but not the late stages of cocaine associative learning while responsiveness of mPFC DA to cocaine-paired stimuli was enhanced with extended conditioning experience. The results indicate that brain areas responsive to conditioned stimuli transfers as associative learning progresses. These findings suggest that a dynamic role of DA in distinctive brain regions should be taken into account during treatment and relapse prevention of cocaine addiction.Item Involvement of mu-opiate receptors in ethanol-induced accumbal dopamine response(2003-08) Tang, Man Amanda, 1972-; Gonzales, Rueben AnthonyThe goal of this dissertation was to investigate the role of µ-opiate receptors in the regulation of ethanol-induced accumbal dopamine release using µ-opiate receptor knockout mice. Accumbal dopamine response to ethanol (2 g/kg, intraperitoneal injection, i.p.) was characterized in one of the parental strains that the knockout mice were developed on, C57BL/6; two strains of µ-receptor knockout mice (C57BL/6 x 129SvEv, C57BL/6 background); and the mixed genetic background mice pretreated with µ1-receptor antagonist, naloxonazine. Ethanol increases accumbal dopamine release in both male and female C57BL/6 mice. Thus, the C57BL/6 strain is a justifiable model system for studying the mechanisms involved in ethanol regulation of mesolimbic dopamine activity. Habituation to the i.p. procedure is required to detect a significant increase in accumbal dopamine response compared with saline controls in males. Therefore, it was routinely used for the remaining experiments. Accumbal dopamine response to ethanol was abolished in female, not in male knockout mice (C57BL/6 x 129SvEv). Similar results were obtained in the mixed genetic background mice that were pretreated with naloxonazine. The similarity of the results from the naloxonazine study to that of the knockout model suggests the absence of neurochemical compensations due to gene deletion. Finally, a decrease in accumbal dopamine release induced by ethanol was observed in both male and female knockout mice (C57BL/6). The gender difference seen in the mixed genetic background knockout mice may be due to the influence of one of the parental strains, 129SvEv, on the hybrid strain of the knockout mice. The results with both gene deletion and pharmacological blockade of the µ- opiate receptor support the hypothesis that µ-opiate receptors are a critical component of the mechanism by which ethanol stimulates accumbal dopamine release.