Behavioural Brain Research 196 (2009) 237–241 Contents lists available at ScienceDirect Behavioural Brain Research journal homepage: www.elsevier.com/locate/bbr Research report Analgesic, learning and memory and anxiolytic effects of insulin in mice Moses A. Akanmu ∗ , Nwamaka L. Nwabudike, O.R. Ilesanmi Department of Pharmacology, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun-state, Nigeria article info Article history: Received 7 March 2007 Received in revised form 31 August 2008 Accepted 9 September 2008 Available online 18 September 2008 Keywords: Insulin Analgesic Locomotor Memory Anxiety Mice abstract Insulin is a polypeptide hormone that is present in mammals and its main function is the mainte- nance of adequate blood sugar level. Insulin receptors are widely but unevenly distributed in the brain. Insulin has been reported to be involved in the regulation of neurotransmitters release. It has also been linked to the pathogenesis of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Although there is abundant literature on the study of biochemical and molecular properties of insulin, there has been no literature on its central behavioural effects on anxiety and pain relief among other behavioural effects. This study therefore investigates whether insulin has any anxiolytic and other CNS effects. This experiment was carried out in mice using animal behavioural models including a hot plate analgesic test, holeboard and elevated plus maze for anxiolytic test. A Y-maze was used for the locomotor activity and spontaneous alternation investigations. Mice were administered intraperitoneally with insulin at different doses of 0.5, 1.0 and 2.0IU/kg. The results obtained showed that insulin has no analgesic activity, however, it caused significant central inhibitory effects by decreasing both locomotor activity in both holeboard and Y-maze models and also decreased the exploratory behaviour in holeboard at doses administered dose-dependently indicating its sedative effects. In elevated plus maze, insulin had no effects on percentage of open arm entries at all doses but had a significant effect on percentage of open arm duration at the dose of 1.0 IU/kg only. Insulin administration at lower doses (0.5 and 1.0IU/kg, i.p.) had no effect on spatial working memory, however, it had significant spatial working memory impairment at the dose of 2.0 IU/kg, i.p. in mice. The study showed that insulin has several neuropharmacological effects at doses used. © 2008 Elsevier B.V. All rights reserved. 1. Introduction Insulin is an acidic proteinous hormone having a molecular weight of approximately 5600. This hormone is composed of two polypeptides called A and B chains which are covalently joined by two intrachain disulfide bonds. A third intrachain disulfide bridge is present in the A chain. The chains are formed by proteolysis of pro-insulin, a larger single chain precursor, by removal of the intervening sequence of amino acids, referred to as the C-peptide. Insulin is essential for metabolic processes involving carbohydrates, fats and proteins. In most tissues, insulin stimulates the uptake of glucose, fatty acids and amino acids and aids their eventual con- version into storage forms. Naturally, higher animals produce their own endogenous insulin from the pancreas. Today there are various types of insulin, which are classed based on their onset of action, peak time and duration of action. Insulin is used in the management of diabetes mellitus, where there is either a lack of insulin produc- ∗ Corresponding author. Tel.: +234 8035958466. E-mail address: maoakanmu@yahoo.com (M.A. Akanmu). tion or non-sensitivity of the -cells of the pancreas to produce insulin. The existence of insulin receptors within the brain is less well known and the functions of these receptors are somewhat an enigma. It is important to note that brain cells are not fully reliant upon insulin for glucose supply, they have independent means of obtaining glucose. Also, brain insulin receptors (InsRb) differ some- what from their peripheral counterparts [1]. The physiological role of insulin receptors in the brain appears to be twofolds: (1) the tight control of glucose transport in specific brain regions and (2) the yet incompletely understood function in the central nervous system (CNS) development and function. Aberrant function of the brain insulin receptors has been hypothesized to be involved in CNS dysfunction [29]. Even distribution of insulin receptors would be expected throughout the brain particularly if their only function is to mediate insulin-induced glucose transport into neurons as a source of energy. It has been shown that the highest brain-insulin receptor densities are found in the olfactory bulb, cerebral cor- tex, hypothalamus, cerebellum and choroids plexus [1,2,12,16,33]. Furthermore, high densities of brain insulin receptors are found in the thalamus, caudate putamen and some mesencephalic and 0166-4328/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2008.09.008