title: Low-level repeated exposure to diazinon and chlorpyrifos decrease anxiety-like behaviour in adult male rats as assessed by marble burying behaviour.
abstract: 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 (1 mg/kg i.p.) which is present in sheep dip and flea collars, chlorpyrifos (1 mg/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.
authors: Medical Toxicology Centre, Newcastle University, Claremont Place, Newcastle upon Tyne NE2 4AA, UK; Institute of Neuroscience, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors: Claire Y
authors: CY
authors: Savy
authors: Medical Toxicology Centre, Newcastle University, Claremont Place, Newcastle upon Tyne NE2 4AA, UK; Institute of Neuroscience, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors: Ann E
authors: AE
authors: Fitchett
authors: Institute of Neuroscience, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors: Richard
authors: R
authors: McQuade
authors: Institute of Neuroscience, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors: Sarah E
authors: SE
authors: Gartside
authors: Medical Toxicology Centre, Newcastle University, Claremont Place, Newcastle upon Tyne NE2 4AA, UK; Institute of Neuroscience, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors: Christopher M
authors: CM
authors: Morris
authors: Medical Toxicology Centre, Newcastle University, Claremont Place, Newcastle upon Tyne NE2 4AA, UK; Institute of Neuroscience, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors: Peter G
authors: PG
authors: Blain
authors: Medical Toxicology Centre, Newcastle University, Claremont Place, Newcastle upon Tyne NE2 4AA, UK; Institute of Neuroscience, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. Electronic address: s.j.judge@ncl.ac.uk.
authors: Sarah J
authors: SJ
authors: Judge
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004390:Chlorpyrifos / Q000494:pharmacology / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D003976:Diazinon / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D055664:Electrochemical Techniques; D005106:Exploratory Behavior / Q000187:drug effects*; D005518:Food Preferences / Q000187:drug effects; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats
chemical_list: D014151:Anti-Anxiety Agents; D018377:Neurotransmitter Agents; D000110:Acetylcholinesterase; D004390:Chlorpyrifos; D003976:Diazinon
keywords: 5-HT; Anxiety; Depression; Organophosphate; Pesticide; Serotonin