Statins modify the response of chicks to challenges with xylazine-ketamine and carbaryl

Statins are known to affect brain function in a manner not related to their dyslipidemic effects. The purpose of the present study was to assess the behavioral response of a chick model (7-14 days old) after single treatments with the statins atorvastatin, fluvastatin or simvastatin at 100 mg/kg, orally, to a pharmacological challenge with an anesthetic regimen of xylazine (5 mg/kg)-ketamine (20 mg/kg), intramuscularly, and a toxicological challenge with the reversible cholinesterase inhibiting insecticide carbaryl (250 mg/kg, orally). Only simvastatin significantly reduced the duration of xylazine-ketamine anesthesia by 47%. Carbaryl at 250 mg/kg, orally induced signs of cholinergic poisoning (57.1 - 100%) in chicks within 3.14 min, and 57.1% death occurred within 85 min. Toxicological challenge of statin-treated chicks with carbaryl also induced signs of cholinergic poisoning, but with varying percentages of reductions compared to the control (carbaryl) group. The reductions in 4 h carbaryl-induced lethality in chicks pre-treated with atorvastatin, fluvastatin and simvastatin were 43, 57 and 29%, respectively, below that of the control value. Correspondingly, their toxicity scores decreased by 18, 18 and 11%, respectively. These data suggest that statins might modulate the functional status of the brain in a manner that affects the impact of centrally acting drugs or toxicants, and hence the behavioral outcomes in chicks. Further studies are warranted on the behavioral effects of statins after prolonged therapy.