Relationship between the Dose to Produce Reinforcing Effect and that of Gross Behavioral Effects in Rhesus Monkeys

The selection of an appropriate range of doses is critical in drug self-administration, since the number of self-administrations and dose levels of a drug is interrelated, forming an inverted U-shape. The purpose of this study was to investigate the relationship between the dose to produce the reinforcing effect and that of gross behavioral effects, in order to determine dose ranges of a drug to assess the reinforcing effect. For assessing the reinforcing effect, the dose that was most frequently self-administered was explored in intravenous self-administration experiments in rhesus monkeys under a fixed ratio 5 schedule with a 1 min timeout after each self-administration for 2 h daily. For the gross behavioral effects, the minimum effective dose following cumulative dosing was observed. The most frequently self-administered dose levels were 0.016 and 0.064 mg/kg/infusion in cocaine, 0.25 and 0.5 mg/kg/infusion in pentobarbital, 0.016 and 0.063 mg/kg/ infusion in pentazocine, 0.001 and 0.004 mg/kg/infusion in nicotine and 0.256 mg/kg/infusion in caffeine. These dose levels were 1/250-1/8 of the minimum effective doses in gross behavioral observations. Thus, it is suggested that a broad dose-range, less than the minimum effective doses in the gross behavioral observations, should be used in intravenous self-administration experiments for assessing the reinforcing effect of a drug.