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Muscarinic M1, M3, Nicotinic,GABAA and GABAB Receptor ...

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1995). As reported by McNay et al 2006 recurrently hypoglycemic rats required<br />

progressively less insulin to achieve hypoglycemia, presumably due to the loss of<br />

the counterregulatory response. Low blood glucose levels are associated with<br />

negative mood states, primarily self-reported ‘‘nervousness” (Boyle <strong>and</strong> Zrebiec,<br />

2007). Moreover, patients with a history of severe hypoglycemia show<br />

significantly increased levels of anxiety (Wredling et al., 1992) or ‘‘negative<br />

mood” (Gonder-Frederick et al., 2008) relative to other patients with IDDM. The<br />

prolonged effects of even mild hypoglycemia on subsequent counter regulation<br />

underline the importance of scrupulously avoiding even mild hypoglycemic<br />

episodes in patients with diabetes. The body weights of D + IIH <strong>and</strong> C + IIH rats<br />

showed no significant change compared to control while they showed significant<br />

increased weight compared to diabetic. The initiation of insulin therapy in diabetes<br />

is usually associated with weight gain (Wing et al., 1990).<br />

In the study, both hypoglycemic groups showed increased circulating<br />

insulin level. Alterations in circulating insulin levels <strong>and</strong> insulin signaling<br />

pathways due to diabetes <strong>and</strong> its treatment directly affect the brain (Biessels et al.,<br />

2004). Insulin affects multiple mechanisms related to neuronal activity. Although<br />

hyperinsulinemia does not affect whole-brain glucose use, hyperinsulinemia in<br />

rats changed glucose metabolism in the brain regions Hyperinsulinemia has been<br />

reported to antagonize the stimulatory effect of epinephrine on hepatic glucose<br />

production (Moan et al., 1995).<br />

BEHAVIOURAL DEFICITS IN EXPERIMENTAL RATS<br />

We evaluated the behavioural response of experimental rats in Y-maze<br />

test which is used to evaluate the spatial learning in different rat models<br />

(Murugesan, 2005). Also, motor performance of control <strong>and</strong> experimental rats on<br />

grid walk test were studied. Clinical <strong>and</strong> animal studies suggest that recurrent<br />

hypoglycemia leads to persistent behavioral <strong>and</strong> cognitive impairments (Wredling<br />

et al., 1990; Gold et al., 1993; Akyol et al., 2003).<br />

101

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