M2 muscarinic autoreceptors modulate acetylcholine release in prefrontal cortex of C57BL/6J mouse

Muscarinic autoreceptors modulate cholinergic neurotransmission in animals ranging from insects to humans. No previous studies have characterized auto receptor modulation of acetylcholine (ACh) release in prefrontal cortex of intact mouse. Data obtained from experiments in 45 mice considered ACh as a phenotype and tested the hypothesis that pharmacologically defined M2 rece ptors modulate ACh release in prefrontal cortex of C57BL/6J mouse. In vivo microdialysis quantified ACh release during delivery of Ringer's (control) or Ringer's containing muscarinic receptor antagonists. The lowest concentr ation of each antagonist [scopolamine, pirenzepine, or 11-2[(-[(di-ethylami no)methyl]-1-piperidinyl)-acetyl]-5,11-dihydro-6H-pyrido(2,3-b)(1,4)-benzod iazepine-one (AF-DX116)] that significantly increased ACh release was deter mined and defined as the minimum ACh-releasing concentration. Dialysis deli very of scopolamine caused a concentration-dependent increase in ACh releas e, consistent with the existence of muscarinic autoreceptors. The order of potency for causing increased ACh release was scopolamine = AF-DX116 > pire nzepine. Administration of pertussis toxin into prefrontal cortex blocked t he AF-DX116-induced increase in ACh release. These findings support the con clusion that M2 receptors modulate ACh release in C57BL/6J mouse prefrontal cortex. Nearly every human gene has a mouse homolog and the appeal of mous e models is reinforced by the identification of mouse genes causing phenoty pic deviants. The present data encourage comparative phenotyping of cortica l ACh release in additional mouse strains.