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

The aim of the study was to analyse in a well-established model of neophobi a the effects of peripheral and central (ICV) administration of a prototypi cal and easily penetrating to the brain acetylcholinesterase inhibitor (ACh E-I) - physostigmine, hemicholinium, a selective blocker of the high affini ty choline uptake sites, as well as muscarinic and nicotinic receptor ligan ds. Thus, an attempt was made to address the question whether anxiolytic-li ke effects of AChE-I, reported in the clinic, are directly related to the a nti-emotional action. The effects of peripherally and centrally administrat ed cholinergic ligands on novelty-induced decrease in exploratory behaviour were examined in rats. It was found that in a limited dose-range physostig mine and nicotine given peripherally or ICV selectively disinhibited rat ex ploration in the open field, whereas scopolamine stimulated animal motor ac tivity and increased thigmotaxis. Locomotor effects of physostigmine and ni cotine appeared at: the higher doses and could be easily separated from the ir anti-neophobic action. The rat's exploratory behaviour tended to be atte nuated by central administration of hemicholinium (a choline uptake blocker ), and it Mras significantly inhibited by mecamylamine (a nicotinic recepto r antagonist), and pirenzepine (a selective M-1, receptor antagonist). Gall amine, a selective M-2 receptor antagonist, did not influence on animal nov elty-induced anxiety-related behaviour. It is concluded that AChE-I can sel ectively affect brain emotional processes evoked by neophobia-related stimu li. Probably both nicotinic and M-1 cholinergic receptors mediate such an a ction of AChE-I.