Rat Brain Biogenic Amine Levels during Acute and Subacute Phosphamidon Treatment with Reference to Behavioral Tolerance

Abstract

Organophosphate (OP) pesticides exert their toxic effects by cholinesterase inhibition and the consequent prolongation of the undesirable effects of accumulation of acetylcholine. However, sustained cholinesterase inhibition through sustained sub-acute administration of organophosphates leads to disappearance of the initial signs of toxicity, termed behavioral tolerance. The present study examines if the levels of amine neurotransmitter substances in rat brain regions are altered during acute and sub-acute treatment with an organophosphate pesticide. Phosphamidon under different time intervals was used with due reference to behavioral tolerance. Acute (1 day) and sub-acute (1 day, 7 days, 15 days) doses of phosphamidon were administered by oral intubation. Different brain regions were isolated at specific time intervals. The levels of epinephrine (EP), nor-epinephrine (NE), dopamine (DA) and serotonin (5-HT) and the activity levels of the enzyme monoamine oxidase (MAO) were determined at the specified time intervals under both acute and sub-acute dose treatments. The amine levels showed differential variations in different brain regions during acute and sub-acute treatments, implying regional changes in catecholamine and serotonin levels during the development of OP-induced behavioral tolerance. Monoamine oxidase activity was in general inhibited in all the brain regions under both acute and sub-acute treatments. The results indicate the involvement of noncholinergic mechanisms during behavioral tolerance. Key words : Behavioral tolerance, Biogenic amines, Phosphamidon, Rat brain