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

outward conductance resulting in hyperpolarisation. Both responses were
mediated by the activation of GABAA receptors, since they were both mimicked
by the GABAA receptor agonist muscimol and antagonized by picrotoxin and
bicuculline (Labrakakis et al., 1997).
Our study on GAD, the enzyme that catalyzes the decarboxylation of
glutamate to GABA, GABA receptor binding and expression of GABA receptor
subtypes GABAAα1 and GABAB showed significant alterations in the cerebral
cortex region in hypoglycemic rats compared to diabetic. GAD is the rate limiting
enzyme of GABA synthesis and it is used as a marker for GABAergic activity
(Sophie et al., 1990). GAD expression showed significant down regulation in
hypoglycemic group. GABA receptor binding studies revealed decreased Bmax
which showed decreased receptor number eventhough the affinity of the receptor
did not show significant change as shown by no change in Kd. It is reported that in
both epileptic and histologically damaged cortex, there are significant decreases in
GAD and GABA binding (Lloyd et al., 1981). Real time PCR analysis also
showed similar results of GABA receptor binding in the cerebral cortex.
Histological evidence as shown by specific GABAAα1 receptors showed decreased
mean pixel value, which is in accordance with the gene expression study. In
addition to augmentation of endogenous protective mechanisms following
different pathophysiological conditions, alterations in the kinetics and
pharmacology of GABAA receptors is associated with the development of
spontaneous seizure activity (Treiman, 2001; Nishimura et al., 2005).
Studies employing magnetic resonance spectroscopy (MRS) suggest that
unipolar depression is associated with reductions in cortical GABA levels
(Sanacora et al., 1999; 2000). Antidepressant and mood-stabilizing treatments also
appear to raise cortical GABA levels and to ameliorate GABA deficits in patients
with mood disorders (Krystal et al., 2002). Anxiety disorders have long been
associated with disturbances of GABA function because of the ability of the
benzodiazepine anxiolytics to facilitate brain GABA neurotransmission (Honig, et
123