The leopard gecko (Eublepharis macularius) is a reptile species in which embryonic temperature contributes both to sex determination and within- sex polymorphisms. Its life history makes the leopard gecko a model system for seeking ontogenic and proximate explanations for within-sex variation in sexually dimorphic behavior and neurophysiology, necessary attributes for reproductive success. For my dissertation I have incorporated the role of androgens that potentially modulate incubation temperature effects on behavioral and brain variation, which I approached using embryo and adult leopard geckos. First, I found that that the bias of same-sex clutch siblings is primarily incubation temperature- dependent and any maternal or genetic effects on same-sex clutch siblings are secondary. Second, I found that testosterone concentrations in the yolk-albumen were higher in eggs of late development than early development at 26 °C, a female-producing incubation temperature, but did not differ from eggs incubated at another female-biased temperature. This increase in testosterone concentrations during the temperature sensitive period in putative females is a finding opposite of reported trends in most other reptiles studied to date. Further, I found that the embryonic environment influences male sociosexual investigation in the absence of gonadal hormones. Lastly, in adult males of 32.5 °C, a male-biased incubation temperature, I found that the phosphoprotein DARPP-32 that is activated by the D1 dopamine receptor in limbic brain regions is correlated to this sociosexual investigatory behavior. Neurons immunopositive for phosphorylated DARPP-32 were not only less dense in the nucleus accumbens of males who spent more time with other males, but also more dense in the preoptic area of males who spent more time with females. The use of phosphorylated DARPP-32 as marker for sociosexual exposure is novel in a lizard species. Taken together, in support of previous studies, these results show that differences in embryonic environment stem primarily from incubation temperature, can explain behavioral differences in adulthood in the absence of hormones, and, in concert with hormonal manipulation, can influence neuronal marker sensitivity to sociosexual exposure. / text

Indiana University-Purdue University Indianapolis (IUPUI) / Alcohol use disorder (AUD) and nicotine dependence often result in serious health problems and are top contributors to preventable deaths worldwide. Co-addiction to alcohol and nicotine is the most common form of polysubstance abuse. Epidemiological studies indicate that more than 80% of individuals diagnosed with AUD concurrently use nicotine. The prevalence of alcohol and nicotine comorbidity may stem from interconnected mechanisms underlying these disorders. A better understanding of how these drugs interact and the biological basis behind the high comorbidity rates could generate key targets for the development of more effective treatments for AUD and nicotine dependence. The following experiments utilized four similar overall groups consisting of vehicle, ethanol (EtOH), nicotine (NIC), and EtOH+NIC. Chapter Two investigated the efficacy of naltrexone and varenicline, the pharmacological ‘gold standards’ for treating AUD and nicotine dependence, on voluntary drug intake by rats selectively bred for high EtOH drinking. The results indicated that the standard treatments for AUD and nicotine dependence were effective at reducing consumption of the targeted reinforcer but neither reduced EtOH+NIC co-use/abuse. Chapter Three examined the effects of peri-adolescent EtOH drinking on the ability of NIC infused into the posterior ventral tegmental area (pVTA) to stimulate dopamine release within the nucleus accumbens (NAc) shell during adulthood. The results suggest a cross-sensitization to NIC produced by peri-adolescent EtOH consumption demonstrated by a leftward and upward shift in the dose response curve. Chapter Four investigated the effects of intra-pVTA infusions on NAc shell neurochemistry, EtOH reward within the NAc shell, and the role of brain-derived neurotrophic factor (BDNF) on EtOH reward within that region. The data indicated that only EtOH+NIC significantly increased glutamate, dopamine, and BDNF in the NAc shell. Repeated pretreatment with EtOH+NIC also enhanced EtOH reward in the NAc shell and BDNF infusions were sufficient to recapitulate these findings. Collectively, the data indicate that concurrent exposure to EtOH and NIC results in unique neuroadaptations that promote future drug use. The failure to develop effective pharmacotherapeutics for AUD or nicotine dependence could be associated with examining potential targets in models that fail to reflect the impact of polydrug exposure. / 2020-04-03

Projections from the Nucleus Accumbens (NAc) to the Ventral Pallidum (VP) play a critical role in motivation and reward. Rewards and reward-associated cues are thought to alter this pathway by suppressing GABA release to the VP, however, the role of the NAc to VP pathway has never been investigated with regard to nicotine self-administration. We hypothesized that increasing GABAergic signaling from the NAc to the VP would decrease the reinforcing effects of nicotine. To increase GABA release, CRE dependent DREADD was expressed in the NAc of male rats. Administration of low dose clozapine activated the DREADD receptor and showed a reduction in responding for nicotine suggesting that activation of the NAc to VP pathway reduced reinforcement. However, a nonspecific effect was observed leading to future investigation of locomotor activity. Immunohistochemistry and microdialysis were used to confirm DREADD expression in the NAc and increased extracellular GABA in the VP.

Made available in DSpace on 2016-06-02T19:22:56Z (GMT). No. of bitstreams: 1 4388.pdf: 1226815 bytes, checksum: 90cf9ba0ac00628538f6b744e2c5bac1 (MD5) Previous issue date: 2011-02-25 / Financiadora de Estudos e Projetos / Estrogen is a steroid hormone known to play a role in cellular events important for development, maintenance of body physiology and modulatory actions on central nervous system during life. The aim of this study was to investigate the effect of ovariectomy (OVX) and the intervention of strength training on the tissue concentrations of dopamine (DA) and serotonin (5-HT) in the nigrostriatal and mesolimbic pathways in female rats. Also, check behavioral parameters of exploratory activity in novel environment, in testing of the plus maze (EPM) and open field (CA). Female rats were divided into four groups: Sedentary (Sed- Intact), ovariectomized Sedentary (Sed-OVX) Trained intact (Intact-ExCrônico) Trained ovariectomized (OVX-ExCrônico) (n = 10 per group). We conducted a period of 12 weeks of strength training which consisted of increases in a vertical ladder of 1.1 meters, weight tied to its tail. The sessions were held once every three days with 4-9 and 8-12 uphill climb for motion. The OVX caused changes in tissue concentrations of DA and 5-HT in the mesolimbic and nigrostriatal pathways. However strength training has not been able to revet these changes. In behavioral tests of anxiety were observed behavior and decrease the exploratory activity of rats in the independent training (OVX). The results of this study showed that OVX alters the state of the tissue concentrations of DA and 5-HT but these changes seem to depend on the type of receptor and its topographic distribution. Strength training has not been able to reverse these changes. / O estrogênio é um hormônio esteróide conhecido por representar um papel relevante nos eventos celulares do desenvolvimento, manutenção da fisiologia do corpo e ações moduladoras no sistema nervoso central (SNC) durante a vida. O objetivo do presente estudo foi investigar o efeito da ovariectomia (OVX) e da intervenção do treinamento de força sobre as concentrações teciduais de dopamina (DA) e serotonina (5- HT) nas Vias Nigroestriatal e Mesolímbicas em ratas. Além disso, verificar parâmetros comportamentais de atividade exploratória em ambiente novo, nos testes do labirinto em cruz elevado (LCE) e campo aberto (CA). Ratas fêmeas foram divididas em quarto grupos: Sedentário (Sed-Intacto); Sedentário ovariectomizado (Sed-OVX); Treinado intacto (ExCrônico-Intacto); Treinado ovariectomizado (ExCrônico-OVX) (n = 10 por grupo). Foi realizado um período de 12 semanas de treinamento de força que consistia em subidas em uma escada vertical de 1,1 metros, com peso atado a cauda. As sessões foram realizadas uma vez a cada três dias com 4-9 subidas e 8-12 movimentos por escalada. A OVX causou alterações na concentração tecidual de DA e 5-HT nas Vias Mesolímbica e Nigroestriatal . No entanto o treinamento de força não foi capaz de reverter essas alterações. Nos testes comportamentais foi observado comportamento de ansiedade e decréscimo da atividade exploratória dos animais submetidos ao treinamento, independente da OVX. Os resultados deste estudo mostram que o estado de OVX altera as concentrações teciduais de DA e 5- HT, no entanto essas alterações parecem depender do tipo de receptor e da sua distribuição topográfica. O treinamento de força não foi capaz de reverter essas alterações.

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