Subacute oral administration of codeine causes upward regulation of pro-apoptotic genes in fore brain tissue of rabbits

Abstract

Addictive drugs trigger strong and persistent neuroadaptive changes in the brain through a series of gene regulatory mechanisms leading to addiction. The objective of the study was to assess the effect of 28day oral administration of codeine on the expression of anti-apoptotic (Bcl-2) and pro-apoptotic (Bax) genes in the frontal lobe of the brain of adult rabbits. Dihydrocodeine tablets were obtained from the National Drug Law Enforcement Agency (N.D.L.E.A) and subjected to cold water extraction method to separate the active ingredient from other formulation excipients. Twenty-four adult rabbits that were priory acclimatized for ten days, were divided into four groups of six each. The first three groups were tagged as experimental while the fourth as control group. The three experimental groups were orally administered with graded doses of codeine of 3mg/kg (low dose),5mg/kg (medium dose) and 7mg/kg (high dose) respectively for 28 days, while the fourth group (the control group) were given distilled water only .On the 29th day, biological sampling of two rabbits from each group was done, and the experimental animals were humanely sacrificed . Frontal brain tissues were obtained from each rabbit and subjected to gene expression analysis using standard methods. Gene of interest were Bax and Bcl-2. Molecular analysis for pro apoptotic gene (bax) in the frontal lobe showed a highly significant increase at low-dose and high-dose rabbits relative to control. For the anti-apoptotic gene Bcl-2 however, there was a highly significant decrease in the frontal lobe of the brain of medium and high dose groups respectively, it was concluded that codeine causes upward regulation of pro apoptotic gene (bax) and downward regulation of anti-apoptotic gene (Bcl-2) in the rabbit forebrain.