The effects of physostigmine and cholinergic receptor ligands on novelty-induced neophobia

Abstract

The aim of the study was to analyse in a well-established model of neophobia the effects of peripheral and central (ICV) administration of a prototypical and easily penetrating to the brain acetylcholinesterase inhibitor (AChE-I)--physostigmine, hemicholinium, a selective blocker of the high affinity choline uptake sites, as well as muscarinic and nicotinic receptor ligands. Thus, an attempt was made to address the question whether anxiolytic-like effects of AChE-I, reported in the clinic, are directly related to the anti-emotional action. The effects of peripherally and centrally administrated cholinergic ligands on novelty-induced decrease in exploratory behaviour were examined in rats. It was found that in a limited dose-range physostigmine and nicotine given peripherally or ICV selectively disinhibited rat exploration in the open field, whereas scopolamine stimulated animal motor activity and increased thigmotaxis. Locomotor effects of physostigmine and nicotine appeared at the higher doses and could be easily separated from their anti-neophobic action. The rat's exploratory behaviour tended to be attenuated by central administration of hemicholinium (a choline uptake blocker), and it was significantly inhibited by mecamylamine (a nicotinic receptor antagonist), and pirenzepine (a selective M1 receptor antagonist). Gallamine, a selective M2 receptor antagonist, did not influence on animal novelty-induced anxiety-related behaviour. It is concluded that AChE-I can selectively affect brain emotional processes evoked by neophobia-related stimuli. Probably both nicotinic and M1 cholinergic receptors mediate such an action of AChE-I.

Fluoxetine Disrupts the Integration of Anxiety and Aversive Memories

“…Other studies in part support the results obtained with pirenzepine, by demonstrating that blockade of M1, but not M2, muscarinic receptors in the hippocampus modulates anxiety levels (File et al, 1998;Sienkiewicz-Jarosz et al, 2000). On the other hand, some other work, including data from our own laboratory, has previously shown that increasing cholinergic tone may decrease anxiety (Degroot and Treit, 2003;File et al, 1998).…”

Phospholipase C β4 in the Medial Septum Controls Cholinergic Theta Oscillations and Anxiety Behaviors

“…Thus, the lower the index, the higher the thigmotaxis. The thigmotaxis index was calculated for each mouse separately and used to calculate means and SEMs for a given experimental group (Treit and Fundytus, 1988;Sienkiewicz-Jarosz et al, 2000).…”

The expression level of muscarinic M1 receptor subtypes in different regions of rat brain

“…Many studies have confirmed that blockade of M 1 receptors, in the dorsal hippocampus lower the anxiety [24,25]. Although, FLU were found to be effective in decreasing the anxiety state, FLU at 10 mg/kg was found to be ineffective.…”