Comparison of the antinociceptive activity of intraventricularly administered acetylcholine to narcotic antinociception.

Intraventricularly administered acetylcholine inhibits mouse tail-flick latency in a dose-dependent manner with an ED50 of about 20 microgram. This antinociceptive activity is not mimicked by biogenic amine neurotransmitters (i.e. norepinephrine, epinephrine, dopamine, serotonin or histamine) and is not markedly affected by selective depletors of brain catecholamines or serotonin. However, pretreatment with reserpine or tetrabenazine dramatically reduces acetylcholine-induced antinociception. Tolerance develops rapidly to the antinociceptive effects of acetylcholine. Cross-tolerance to morphine in acetylcholine-tolerance mice is minimal, but the antinociceptive activity of acetylcholine is markedly reduced in mice chronically pretreated with morphine. Acetylcholine-induced antinociception differs from narcotic antinociception in the reversed stereoselectivity of several narcotic antagonists and in the in vivo pA2 values for inhibition by naloxone. Therefore, the antinociceptive activity of intraventricularly administered acetylcholine cannot be described as a specific narcotic action.