The Journal of pharmacology and experimental therapeutics
-
J. Pharmacol. Exp. Ther. · Jul 1981
Barbiturates: active form and site of action at node of Ranvier sodium channels.
Barbiturate sodium channel block was investigated in the voltage-clamped amphibian node of Ranvier. Internal pH was manipulated by diffusion of buffers from the cut internodes. Like local anesthetics and volatile general anesthetics, barbiturates shift the voltage dependence of inactivation in the hyperpolarizing direction. ⋯ Unlike local anesthetics, however, phenobarbital exerts a frequency-dependent block which is modified by changes in internal pH and is not affected by changes in external pH. In addition, barbiturate frequency dependence is apparently more exclusively involved with channel inactivation. The results suggest a barbiturate sodium channel binding site closer to the axoplasm than the local anesthetic binding site is and also suggest that there is a proton barrier between the two sites.
-
J. Pharmacol. Exp. Ther. · Jul 1981
Fixed-ratio responding under second-order schedules of food presentation or cocaine injection.
Squirrel monkeys pressed a key under second-order schedules in which every nth response resulted in a 2-sec visual stimulus (n-response fixed ratio; n = 10, 20 or 30); after a minimum fixed-interval of time elapsed (second-order t-min fixed-interval; t = 5 or 60), the completion of a fixed-ratio resulted in both the brief stimulus and either presentation of food or i.v. injection of cocaine. Under a second-order 5-min fixed-interval schedule with 15 intervals per session, rates of responding increased to a maximum and then decreased with increases in the amount of food (from 250 to 4000 mg/presentation) or cocaine (from 25 to 400 micrograms/kg/injection). Cocaine injections maintained higher maximal rates of responding than food presentation. ⋯ Under a second-order 60-min fixed-interval with one interval per session, both food and cocaine maintained relatively high rates of responding even with large amounts of food (7.5-14 g/presentation) or cocaine (375-1500 micrograms/kg/injection). When the brief stimuli were omitted during the 60-min interval, rates of responding maintained by either food or cocaine decreased. Thus, the brief-stimulus presentations were essential for maintaining performance under the second-order 60-min fixed-interval schedule.