Septal GABAergic and hippocampal cholinergic systems modulate anxiety in the plus-maze and shock-probe tests

According to Gray [The neuropsychology of anxiety: an inquiry into the function of the septo-hippocampal system. Oxford: Oxford Univ. Press, 1982; Neural systems, emotion and personality. In: Madden VJ, editor. Neurobiology of learning, emotion, and affect. New York: Raven Press, 1991. p. 273-306.] the septum and hippocampus act in concert to control anxiety. In the present study we examined the roles of these structures in two animal models of anxiety: the elevated plus-maze and the shock-probe burying tests. We found that microinfusions (20 ng/0.4 microl) of the GABA(A) agonist muscimol into either the lateral or the medial septum increased rats' open-arm exploration in the plus-maze test, and decreased their burying behavior in the shock-probe test. We also found that infusions of the acetylcholinesterase inhibitor physostigmine (10 microg/microl) into the dorsal hippocampus, like intraseptal muscimol (20 ng/0.4 microl), increased open-arm exploration in the plus-maze test, and decreased burying behavior in the shock-probe test. Although combined infusions of intraseptal muscimol and intrahippocampal physostigmine did not increase the magnitude of anxiolysis, this may have been due to "ceiling" effects. Overall, the results confirm that septal GABAergic and hippocampal cholinergic systems are both involved in the modulation of anxiety.