Low-level repeated exposure to diazinon and chlorpyrifos decrease anxiety-like behaviour in adult male rats as assessed by marble burying behaviour

• Published in: Neurotoxicology (Park Forest South) 2015-09, Vol.50, p.149-156
• Main Authors: Savy, Claire Y., Fitchett, Ann E., McQuade, Richard, Gartside, Sarah E., Morris, Christopher M., Blain, Peter G., Judge, Sarah J.
• Format: Article
• Language: English
• Subjects: 5-HT; Acetylcholinesterase - metabolism; Analysis of Variance; Animals; Anti-Anxiety Agents - therapeutic use; Anxiety; Anxiety - drug therapy; Anxiety - physiopathology; Brain - drug effects; Brain - metabolism; Chlorpyrifos - pharmacology; Chlorpyrifos - therapeutic use; Chromatography, High Pressure Liquid; Depression; Diazinon - pharmacology; Diazinon - therapeutic use; Disease Models, Animal; Electrochemical Techniques; Exploratory Behavior - drug effects; Food Preferences - drug effects; Male; Memory, Short-Term - drug effects; Motor Activity - drug effects; Neurotransmitter Agents - metabolism; Organophosphate; Pesticide; Rats; Serotonin
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2015.08.010

•Low-level diazinon exposure attenuated anxiety-like marble burying behaviour.•Diazinon-induced changes in behaviour persisted after exposure cessation.•Low-level diazinon exposure decreased 5-HT transporter expression.•Low-level chlorpyrifos exposure decreased dopamine levels. Occupational exposure to organophosphate (OPs) pesticides is reported to increase in the risk of developing anxiety and depression. Preclinical studies using OP levels, which inhibit acetylcholinesterase activity, support the clinical observations, but little is known of the effects of exposure below this threshold. We examined the effects of low level OP exposure on behaviours and neurochemistry associated with affective disorders. Adult rats were administered either diazinon (1mg/kg i.p.) which is present in sheep dip and flea collars, chlorpyrifos (1mg/kg i.p.) which is present in crop sprays, or vehicle for 5 days. OP exposure did not affect acetylcholinesterase activity (blood, cerebellum, caudate putamen, hippocampus, prefrontal cortex), anhedonia-like behaviour (sucrose preference), working memory (novel object recognition), locomotor activity or anxiety-like behaviour in the open field arena. In contrast OP exposure attenuated marble burying behaviour, an ethological measure of anxiety. The diazinon-induced reduction in marble burying persisted after exposure cessation. In comparison to vehicle, dopamine levels were lowered by chlorpyrifos, but not diazinon. 5-HT levels and turnover were unaffected by OP exposure. However, 5-HT transporter expression was reduced by diazinon suggesting subtle changes in 5-HT transmission. These data indicate exposure to occupational and domestic OPs, below the threshold to inhibit acetylcholinesterase, can subtly alter behaviour and neurochemistry.