A total 31 psychoactive drugs were offered to groups of naive rats for IV self-administration and an injection rate greater than that for rats offered only saline indicated reinforcement. Two protocols were used: in the first, rats were offered drug at a selected dose for 5 days, then the dose was reduced by 1 log unit (to 0.1 the original dose) for an additional 4 days; in the second, rats were offered saline for 3 days as a "prescreen' to eliminate rats with high or low operant-injection rates. Drug was offered to acceptable rats for 5 days, then the dose was reduced 0.5 log unit (to 0.32 the original dose) for 5 more days. A scoring system, based upon the injection rates during the last 3 days of each period, describes the reinforcing action. Scores were dose-related. Tests on both protocols gave similar results. Data from monkey studies have been reported for 27 of the drugs tested. Of these drugs, 18 were reinforcers and six were nonreinforcers in both species, nalorphine and ethylketazocine were reinforcers only in rats, and ethanol was a reinforcer only in monkeys.

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hydrolysis. However, the maximum increase in the PI hydrolysis was significantly (P < 0.01) less than oxotremorine and RS 86. lntraperitoneal administration of U-80816 dose-dependently increased striatal acetylcholine (ACh) concentration, and the effect was significant ( P < 0.01) at 30 mg/kg. In the presence of hemicholinium-3 (HC-3), U-80816 inhibited the release of (3H)-ACh from hippocarnpal slices. On the other hand, in the presence of eserine, U-80816 increased the release of (3H)-ACh. In in vivo pharmacological tests, U-80816 produced hypothermia and tremors in mice. This compound failed to produce lacrimation or salivation in mice when administered up to 100 mg/kg. U-80816 antagonized oxotremorineinduced salivation. It is bioavailable to the brain in a significant amount after oral adminis- tration and has a sufficiently long duration of action. The in vitro and in vivo pharmacological investigations indicate that U-80816 is a partial agonist of muscarinic receptors.