Lack of CB 1 receptors increases noradrenaline release in vas deferens without affecting atrial noradrenaline release or cortical acetylcholine release

We studied whether cannabinoid CB 1 receptor gene disruption (to yield CB 1 −/− mice) affects the electrically evoked tritium overflow from vas deferens and atrial pieces preincubated with [ 3 H]‐noradrenaline (NA) (‘noradrenaline release’) and from cerebral cortex slices preincubated with [ 3 H]‐choline (‘acetylcholine release’). NA release was higher by 37% in vas deferens from CB 1 −/− mice than in vas deferens from CB 1 +/+ mice. The cannabinoid receptor agonist WIN 55,212‐2 inhibited, and the CB 1 receptor inverse agonist/antagonist SR 141716, increased NA release in vas deferens from CB 1 +/+ mice without affecting it in vas deferens from CB 1 −/− mice. Atrial NA release did not differ between CB 1 +/+ and CB 1 −/− mice nor did WIN 55,212‐2 affect NA release in either strain. Cortical acetylcholine (Ach) release did not differ between CB 1 +/+ and CB 1 −/− mice. WIN 55,212‐2 inhibited, but SR 141716 did not affect, Ach release in the cortex from CB 1 +/+ mice. Both drugs did not alter Ach release in the cortex from CB 1 −/− mice. Tritium content did not differ between CB 1 +/+ and CB 1 −/− mice in any preparation. In conclusion, the increase in NA release associated with CB 1 receptor deficiency in the vas deferens, which cannot be ascribed to an alteration of tritium content of the preparations, suggests an endogenous tone at the CB 1 receptors of CB 1 +/+ mice in this tissue. Furthermore, the effect of WIN 55,212‐2 on NA release in the vas deferens and on cortical Ach release involves CB 1 receptors, whereas the involvement of non‐CB 1 –non‐CB 2 receptors can be excluded.British Journal of Pharmacology (2003) 140 , 323–328. doi: 10.1038/sj.bjp.0705449