Propoxur-induced acetylcholine esterase inhibition and impairment of cognitive function: Attenuation by Withania somnifera.

Propoxur (2-isopropoxyphenyl N-methylcarbamate) is widely used as an acaricide in agriculture and public health programs. Studies have shown that sub-chronic exposure to propoxur can cause oxidative stress and immuno-suppression in rats. Carbamates are also known to exhibit inhibitory effect on cholinesterase activity, which is directly related to their cholinergic effects. In the present study, the effect of Withania somnifera (Ashwagandha), a widely used herbal drug possessing anti-stress and immuno-modulatory properties was studied on propoxur-induced acetylcholine esterase inhibition and impairment of cognitive function in rats. Male Wistar rats were divided into four groups. Group I was treated with olive oil and served as control. Group II was administered orally with propoxur (10 mg/kg b.wt.) in olive oil, group III received a combination of propoxur (10 mg/kg b.wt.) and W. somnifera (100 mg/kg b.wt.) suspension and group IV W. somnifera (100 mg/kg b.wt.) only. All animals were treated for 30 days. Cognitive behaviour was assessed by transfer latency using elevated plus maze. Blood and brain acetylcholine esterase (AChE) activity was also assessed. Oral administration of propoxur (10 mg/kg b.wt.) resulted in a significant reduction of brain and blood AChE activity. A significant prolongation of the acquisition as well as retention transfer latency was observed in propoxur-treated rats. Oral treatment of W. somnifera exerts protective effect and attenuates AChE inhibition and cognitive impairment caused by sub-chronic exposure to propoxur.

Behavioral Toxicity of Psychotropic Drugs

Any compound which disrupts the integrity of psychological aspects of performance, in particular, cognitive ability and psychomotor function analogous to the psychological behaviors of routine life, is known to be behaviorally toxic. A significant level of behavioral toxicity will interfere with patient safety and quality of life, and also may be counter-therapeutic by exacerbating the condition that the drug was prescribed for. Now, behavioral toxicity of psychotropic drugs has become one of the main growth areas of psychopharmacological research. Evaluation of the potential of drug-induced behavioral toxicity is important not only to the experimental researcher involved in human psychopharmacology, but also to the clinical practitioner treating psychiatric patients. This article attempts to describe behavioral toxicity of the three classes of psychotropic drugs-benzodiazepines, antidepressants and neuroleptics. After a brief discussion of some methodological issues arising in the investigation of behavioral toxicity, each of these drug classes is reviewed in the context of practical importance rather than purely scientific concern. The last session summarizes some suggestions for future studies on drug-induced behavioral toxicity.