The neonicotinoid insecticide Imidacloprid acts at three pharmacologic
ally distinct acetylcholine receptor (AChR) subtypes in the cockroach
(Periplaneta americana) nervous system, but is ineffective on muscarin
ic receptors. Imidacloprid (3-100 mu mol l(-1)) induced dose-dependent
depolarizations at cockroach cercal afferent/giant interneurone synap
ses. These responses were insensitive to 20 mu mol l(-1) atropine but
were completely blocked by the nicotinic antagonist mecamylamine (50 m
u mol l(-1)). Similarly, Imidacloprid-induced depolarizations of cultu
red cockroach dorsal unpaired median (DUM) neurones dissociated from t
he same (terminal abdominal) ganglion were also completely blocked by
100 mu mol l(-1) mecamylamine. However, two components of the response
could be distinguished on the basis of their differential sensitiviti
es to 0.1 mu mol l(-1) a-bungarotoxin (alpha-BTX), which selectively b
locks AChRs with 'mixed' nicotinic/muscarinic pharmacology in this pre
paration. This indicates that Imidacloprid affects both AChRs sensitiv
e to alpha-BTX and alpha-BTX-insensitive nicotinic acetylcholine recep
tors (nAChRs). Thus, in the cockroach, Imidacloprid activates alpha-BT
X-sensitive synaptic nAChRs in giant interneurones, alpha-BTX-insensit
ive extrasynaptic nAChRs in DUM neurones, and a recently characterized
DUM neurone 'mixed' AChR that is sensitive to both nicotinic and musc
arinic ligands, Imidacloprid does not act on muscarinic acetylcholine
receptors (mAChRs) present on DUM neurone cell bodies and at the cerea
l afferent/giant interneurone synapses. This study shows that Imidaclo
prid can act on pharmacologically diverse nAChR subtypes.