Thesis (Ph.D.) -- University of Adelaide, Dept. of Medicine, 1999. / Bibliography: leaves 181-233.

Thesis (Ph. D.)--Auburn University, 2008. / Abstract. Vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Sydney, 2009. / Title from title screen (viewed June 1, 2009) Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Department of Pharmacology, Faculty of Medicine. Degree awarded 2009; thesis submitted 2008. Third "a" in "GABAA" on t.p. is a subscript. Includes bibliography. Also available in print form.

Thesis (Ph. D.)--Michigan State University. Dept. of Comparative Medicine and Integrative Biology, 2008. / Title from PDF t.p. (viewed July 31, 2009). Includes bibliographical references (p. 165-198). Also issued in print.

Universiẗat, Diss., 2003--München.

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 87-97).

Nicotine (NIC) abuse involves activation of midbrain dopamine (DA) neurons and NIC addiction involves neuroadaptive changes in the mesolimbic DA reward system. GABA neurons in the midbrain ventral tegmental area (VTA) express α4β2-containing nicotinic acetylcholine receptors (nAChRs), whose activation increases GABAergic input to DA neurons. However, this initial effect is decreased after chronic NIC treatment (as in the case of smokers) by inducing nAChR desensitization. Thus, GABA neuron inhibition results in increased DA release in limbic structures such as the nucleus accumbens. To support this hypothesis, we evaluated the effects of acute and chronic NIC on GAD-67 positive neurons in the VTA of GAD GFP mice using in vivo and in vitro electrophysiological methods. In in vivo studies in naïve mice, stimulation of the peduncopontine tegmental nucleus (PPT) activated VTA GABA neurons orthodromically and antidromically. Orthodromic activation of VTA GABA neuron spikes by PPT stimulation was blocked by the nAChR mecamylamine (1 mg/kg). Acute systemic NIC (0.15-0.5 mg/kg IV) had mixed overall effects on VTA GABA neuron firing rate, but in situ microelectrophoretic application of NIC produced a brisk and consistent enhancement (200-500 %) of VTA GABA neuron firing rate that showed no acute tolerance or sensitization with repeated, periodic current application. Local NIC activation was blocked by systemic administration of mecamylamine. Compared to 12 day chronic saline injections, chronic NIC injections (2 mg/kg IP/day) significantly increased VTA GABA neuron firing rate. In in vitro studies, compared to 12 day chronic saline injections, chronic NIC injections decreased DA neuron firing rate. In addition, chronic NIC increased DA neuron, but decreased GABA neuron GABA-mediated sIPSCs. These findings demonstrate that there is reciprocal innervation between the PPT and VTA and that cholinergic input from the PPT is excitatory on VTA GABA neurons. Moreover, VTA GABA neurons are excited by acute NIC and sensitize to chronic NIC, suggesting that α4β2 nAChR subunits on these neurons may play an important role in the adaptations to chronic NIC. Thus, quantitative molecular studies are ongoing to determine specific alterations in nAChRs on VTA GABA neurons to chronic NIC.

No description available.

We have previously found that the 𝘨𝘢𝘣 operon of 𝘌𝘴𝘤𝘩𝘦𝘳𝘪𝘤𝘩𝘪𝘢 𝘤𝘰𝘭𝘪 is RpoS regulated suggesting that it plays an important role during stationary phase growth. The specific role of the 𝘨𝘢𝘣 operon is metabolism of γ-aminobutyrate (GABA). GABA, a four carbon amino acid, is the product of the glutamate decarboxylase reaction in 𝘌. 𝘤𝘰𝘭𝘪 and can serve as a source of carbon and nitrogen for members of the 𝘌𝘯𝘵𝘦𝘳𝘰𝘣𝘢𝘤𝘵𝘦𝘳𝘪𝘢𝘤𝘦𝘢𝘦. Interestingly, we found that we could isolate GABA utilizing mutants even when they carried mutations that were predicted to abolish gab function. However, we were only able to isolate GABA utilizing mutants in the 𝘳𝘱𝘰𝘚⁺ background. This suggests two additional features of GABA metabolism in 𝘌. 𝘤𝘰𝘭𝘪. One, that the 𝘨𝘢𝘣 operon in 𝘌𝘴𝘤𝘩𝘦𝘳𝘪𝘤𝘩𝘪𝘢 𝘤𝘰𝘭𝘪 is indeed dispensable for GABA utilization. Secondly, other RpoS regulated functions, independent of 𝘨𝘢𝘣-encoded functions, may allow the cell to metabolize GABA Finally, we have also investigated the inducing effects of GABA on 𝘨𝘢𝘣 expression in minimal and rich media and the role of glutamate in osmo-tolerance and acid adaptation. / Thesis / Master of Science (MSc)

Heat stress (HS) induces hyperinsulinemia and hypoglycemia in lactating dairy cows. We hypothesized that γ-aminobutyric acid (GABA) participates in the regulation of this altered glycemic state as it is produced by the pancreatic beta cells and has a stimulatory effect on pancreatic secretion of insulin. Multiparous lactating Holstein cows (n=6; 63.33±2.35 DIM, 3.17±0.40 lactations) were placed in environmentally controlled rooms for four experimental periods: 1) thermoneutral (TN; d 1-5; 18±4°C), 2) TN + hyperinsulinemic-hypoglycemic clamp (HHC; d 6-10), 3) heat stress (HS; d 16-20; 33±4°C), and 4) HS + euglycemic clamp (EC; d 21-25). Cows were milked twice daily, and blood samples were collected once daily via coccygeal venipuncture into heparinized evacuated tubes. Plasma GABA concentrations were determined using a competitive ELISA. The data were analyzed in two ways. The first analysis included data from all treatment periods and yielded no period-based differences in plasma GABA concentrations. In this analysis, plasma GABA was lowly correlated to plasma insulin concentrations (r = -0.29, P<0.01). The second excluded data from HHC and EC periods so that GABA concentrations during TN were directly compared to concentrations during HS. In this analysis, plasma GABA concentrations tended to be higher in TN than HS (16.31±2.14 vs 13.80±2.15 ng/ml, respectively, P = 0.06). Milk production was moderately correlated with plasma GABA (r=0.42, P<0.01) and the average plasma GABA during TN and HS was moderately correlated to baseline glucose levels for those periods (r=-0.57, P=0.05). Furthermore, the percent change in plasma GABA was strongly correlated with the percent change in plasma glucose from TN to HS (r=-0.95, P<0.01). Plasma GABA was again lowly correlated to plasma insulin concentrations (r = -0.35, P = 0.01). While these analyses are not indicative of causality, the results suggest that GABA is involved in the regulation of the altered glycemic state observed during HS. More research is needed to determine its precise role in heat-stressed lactating dairy cattle. / Master of Science / Heat stress causes large annual financial losses for the dairy industry and presents potential welfare issues for dairy cows when they can no longer cope appropriately with their environment. As climate change continues, the intensity and duration of heat stress experienced by dairy cows will increase which will cause the effects of heat stress on the dairy industry, as well as on the wellbeing of dairy cows, to become more significant. For this reason, it is important to understand the physiological processes underlying a cow's adaptive response to heat stress to improve future farm management in a changing climate. It is well documented that heat stressed dairy cows experience an increase in plasma insulin concentrations, as well as a concurrent decrease in plasma glucose concentrations. It is not well understood how or why these changes occur, but ɣ-aminobutyric acid (GABA) is known to be secreted from the same cells that secrete insulin and to have effects on the secretion of insulin, as well as on concentrations of glucose in the blood through effects on pancreatic glucagon secretion. This work began the process of determining the physiological mechanism behind these changed concentrations by determining how plasma GABA changes during heat stress in lactating dairy cows and how those changes are related to other physiological changes observed during heat stress. It was determined that plasma GABA tends to decline during heat stress and is significantly related to milk production, as well as blood glucose concentrations. While these results cannot be taken without more research to imply cause, they do support the idea that GABA plays a role in coordinating the altered glycemic state observed in heat stressed dairy cattle and would be an interesting research target in the future.