Impulsivity as Long-Term Sequelae After Chlorpyrifos Intoxication: Time Course and Individual Differences

Abstract

Chlorpyrifos (CPF) is a common organophosphate (OP) insecticide that has been widely used in agriculture as a pesticide. The primary mechanism of acute toxic action of OPs is initiated by acetylcholinesterase (AChE) inhibition. However, non-AChE targets have also been proposed as alternative that contributes to the acute lethal action and side effects of short or long-term exposure. Recently, we have found that a single dose of 250 mg/kg CPF produces acceleration in acquisition on schedule-induced polydipsia (SIP) procedure 6 months after its administration. Moreover, CPF animals show a higher level of impulsivity in a delay-discounting task 1 year after acute administration, and these effects are potentiated when animals are divided into high (HD) and low (LD) drinkers in SIP. In the present study, rats were injected with a subcutaneous (sc) dose of 250 mg/kg of CPF, and 10 weeks later its effect on delay-discounting task was evaluated. Consequently, these animals were evaluated based on SIP, and divided into two populations (HD and LD) according to their rates of drinking in this task. One year after OP administration, these animals were re-evaluated in a delay-discounting task. Results revealed that the CPF-administered rats prefer immediate reward and show a more impulsive choice, 10 weeks after CPF administration. Furthermore, 1 year after it administration, only animals treated with CPF that are high drinkers on SIP are more impulsive than the rest of the groups Therefore, these data suggest that some individuals are more sensitive to OP intoxication than the others, at least in terms of durability of sequelae.

The Red Blood Cell Acetylcholinesterase Levels of Depressive Patients with Suicidal Behavior in an Agricultural Area

“…In this condition hopelessness may be more associated with suicide than depression [28]. Also we did not find any association between the AChE activity and the impulsivity level of patients, in contrast to studies which reported a relationship between OPs exposure and impulsivity in rats [29]. The variation in impulsivity and depression levels may be caused by OPs exposure dose dependently; this could be established by studies on larger populations.…”

Dose-dependent regional brain acetylcholinesterase and acylpeptide hydrolase inhibition without cell death after chlorpyrifos administration

“…As expected according to the literature (Cañadas et al, 2005;Cardona et al, 2006Cardona et al, , 2011López-Granero et al, 2013;Pope et al, 1992;Sánchez-Santed et al, 2004), no signs of acute toxicity were observed after CPF administration (data not shown), except for a reduction of body weight for the doses of CPF 125 and CPF 250 (F (3,44) = 11.33; p < 0.05).…”

“…Several studies have reported about the relation between cognitive impairments and short-term OPs intoxication (Bushnell and Moser, 2006;Bushnell et al, 2001;López-Crespo et al, 2007;López-Granero et al, 2013). Moreover, we found long-term effects in memory and impulsive behaviour (Cañadas et al, 2005;Cardona et al, 2006Cardona et al, , 2011Sánchez-Santed et al, 2004) in absence of this toxicity and when the AChE activity is restored (Pope et al, 1992). These previous results seem to point to other mechanism, besides AChE inihibion, could explain these long term squeals.…”

“…It is well known that CPF reduces brain AChE activity for a long period and it is restored around ten weeks after treatment (Cardona et al, 2011;Pope et al, 1992). However, such a brain AChE activity recuperation seems to be region-dependent.…”

“…The number of animals used in each study is indicated in the "Procedure" section (see below). istration were chosen based on previous data of our laboratory that showed predictably profound and prolonged cholinesterase inhibition, as well as long term cognitive and emotional effects after the higher dose exposure without acute toxicity (Cañadas et al, 2005;Cardona et al, 2006Cardona et al, , 2011. Others (Levin et al, 2010;Lin et al, 2012;Pope et al, 1991) have worked with subcutaneous exposure for a number of years, and Pope et al (1991) determined the subcutaneous Maximal Tolerated Doses of CPF to be 279 mg/kg, causing extensive inhibition of ChE activity in brain (> 78% of inhibition), plasma (> 80% of inhibition) and erythrocytes (> 80% of inhibition) in adults rats.…”