Postnatal exposure to low doses of Chlorpyrifos induces long-term effects on 5C-SRTT learning and performance, cholinergic and GABAergic systems and BDNF expression

Abstract

Alterations in attention and inhibitory control are common features in several neurological disorders. Environmental factors such as exposure to pesticides have been linked to their appearance. Chlorpyrifos (CPF) is one of the most widely used organophosphate compounds in the world. CPF exposure during development seems to be critical for later behavioral and molecular disruptions during adult ages, although this depends on the specific period of development, where the preweaning period is one of the least studied. Despite the abundant empirical work made in the last decades on developmental CPF exposure, the systematic study of this on attention is sparse, and nonexistent concerning inhibitory control, without a single study on preweaning developmental stages. The present research explored the effects of the exposure to low doses of CPF that do not elicit a significant inhibition of the Cholinesterases during this developmental period on rats' behavior in the five-choice serial reaction time task. Behavioral manipulations (inter-trial interval and stimulus duration), pharmacological manipulations (cholinergic and GABAergic drugs) and brain gene expression analyses were also conducted. Exposure to CPF decreased the locomotor activity and enhanced the learning profile of the female rats, increased the impulsive rates, unmasked by a longer inter-trial interval, hypo-sensitized the cholinergic system and down-regulated the mRNA expression levels of the brain-derived neurotrophic factor in the dorsal striatum of the male rats. This happened without significant inhibition of the brain Acetylcholinesterase. All this new information corroborates that the exposure to a common pesticide at low doses during a key, but under-explored developmental period importantly affects different behaviors, neurotransmitter systems, and molecules that are altered in the main neurological disorders observed nowadays.

Keywords: Attention; Brain-derived neurotrophic factor; Chlorpyrifos; Inhibitory control; Learning; Locomotor activity.