Imidacloprid actions on insect neuronal acetylcholine receptors

The neonicotinoid insecticide Imidacloprid acts at three pharmacologically distinct acetylcholine receptor (AChR) subtypes in the cockroach (Periplaneta americana) nervous system, but is ineffective on muscarinic receptors. Imidacloprid (3-100 μmol l-1) induced dose-dependent depolarizations at cockroach cercal afferent/giant interneurone synapses. These responses were insensitive to 20 μmol l-1 atropine but were completely blocked by the nicotinic antagonist mecamylamine (50 μmol l-1). Similarly, Imidacloprid-induced depolarizations of cultured cockroach dorsal unpaired median (DUM) neurones dissociated from the same (terminal abdominal) ganglion were also completely blocked by 100 μmol l-1 mecamylamine. However, two components of the response could be distinguished on the basis of their differential sensitivities to 0.1 μmol l-1 α-bungarotoxin (α-BTX), which selectively blocks AChRs with 'mixed' nicotinic/muscarinic pharmacology in this preparation. This indicates that Imidacloprid affects both AChRs sensitive to α-BTX and α-BTX-insensitive nicotinic acetylcholine receptors (nAChRs). Thus, in the cockroach, Imidacloprid activates α-BTX-sensitive synaptic nAChRs in giant interneurones, α-BTX-insensitive extrasynaptic nAChRs in DUM neurones, and a recently characterized DUM neurone 'mixed' AChR that is sensitive to both nicotinic and muscarinic ligands. Imidacloprid does not act on muscarinic acetylcholine receptors (mAChRs) present on DUM neurone cell bodies and at the cercal afferent/giant interneurone synapses. This study shows that Imidacloprid can act on pharmacologically diverse nAChR subtypes.