exposure to a High Fat Diet During the Perinatal Period Alters the Effects of Centrally Applied Gabaa Receptor Antagonists on Gastric Motility and Tone in Rats
Open Access
- Author:
- Reagan, Zachary
- Graduate Program:
- Anatomy
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- March 27, 2013
- Committee Members:
- Kirsteen Nairn Browning, Thesis Advisor/Co-Advisor
Renato A Travagli, Thesis Advisor/Co-Advisor
Patricia Mc Laughlin, Thesis Advisor/Co-Advisor - Keywords:
- GABA
DMV
DVC
Gabazine
Bicuculline
NTS
Vagus - Abstract:
- Parasympathetic motor innervation to the stomach originates from preganglionic motor neurons of the dorsal motor nucleus of the vagus (DMV). Studies have demonstrated that an ongoing GABAergic input to DMV neurons plays a major role in regulating vagal efferent output from the DMV. The aim of this study was to investigate whether a perinatal high fat diet (HFD) affects the GABAergic regulation of vagal efferent output to the stomach. Male Sprague Dawley rats were fed a HFD (60% kcal from fat) from embryonic day 13 until experimentation at 12 weeks of age. Miniaturized strain gauges sutured to the ventral surface of the gastric corpus were used to record gastric motility. The GABAA¬ receptor antagonists, bicuculline methiodide (BMI; 25, 50, 100pmol) and gabazine (GBZ; 0.78, 3.125, 6.25pmol) were microinjected (60nl) into the dorsal vagal complex (DVC) and the resulting increase in gastric tone was measured at 10 time points after injection (1-10 min) and averaged. A motility index was used to identify changes in motility response and was measured over two five minute periods before and after drug microinjection. Gastric tone responses were represented as a percentage of maximal stomach contraction induced by i.v. injection of the non-selective muscarinic receptor agonist, bethanecol (50µg/kg; 1ml), which itself was unaffected by diet (19.5±3.0g in control vs 25.5±3.6g in HFD; P>0.05). In control rats, BMI induced a dose-dependent increase in gastric tone (2.2±0.34%, 5.4±1.1% and 9.5±3.5% at 25, 50 and 100pmol, n=6, 7, 3, respectively, P<0.05 for each) and showed a trend towards a dose-dependent increase following the perinatal HFD (5.3±2.2%, 8±4.1% and 9.7±4.7% at 25, 50 and 100pmol, n= 4,5,7, respectively, P<0.06). Similarly, the effect of GBZ to increase gastric tone showed a trend towards dose dependency in control animals (3.65±0.95%, 7.02±2.61% and 14.78±7.8% at 0.78, 3.125 and 6.25pmol, n=5,7,5 respectively). These responses were attenuated in the HFD (4.17±0.8%, 3.3±0.6% and 3.4±0.9% at 0.78, 3.125 and 6.25pmol, n=6,6,4, respectively). Microinjection of BMI increased gastric motility in control and HFD rats with a decrease in magnitude between 25pmol (54.8±9.3%) and 100pmol(26.7±16.5). In summary, our data suggest that exposure to a HFD during the perinatal period alters GABAergic activity within brainstem and in the neural circuits controlling gastric functions, which may contribute to the dysregulation of homeostatic reflexes, including appetite and metabolic regulation.