Brain concentrations of phenobarbital and behavioral activation or depression

Brain concentrations of phenobarbital and its effects on locomotor activity and lever responding for food reinforcement were determined at several intervals following injections into C57BL/6J mice. Phenobarbital either elevated or depressed both types of behavior depending on dose and time after injection. Excitation was noted at times and doses when brain concentration was 9 micrograms-11.5 micrograms/g tissue. Depression was initially noted at approximately 20 micrograms/g tissue. Lever responding was altered when brain concentrations of the drug were lower than those associated with corresponding effects on locomotor activity. Excitatory and depressive effects were most extensive when basal response rates were moderate or high respectively. Hence, whether phenobarbital is excitatory or depressive depends on a complex interaction of brain concentration, rate of ongoing behavior and the stimulus conditions maintaining the behavior.