Intensity of the withdrawal syndrome varies with duration of pentobarbital administration

The effect of three dosage schedules on the expression of a withdrawal syndrome indicative of physical dependence on pentobarbital was determined in male Sprague-Dawley rats. Rats were prepared with an intraperitoneal cannula and were continuously infused with either saline (control) or pentobarbital sodium, using an escalating drug dosage schedule, for either 5 (PB-5), 13 (PB-13) or 20 (PB-20) days. Final doses reached were 500 mg/kg/day (PB-5) and 1000 mg/kg/day (PB-13). PB-20 rats reached 1000 mg/kg/day on day 13 and were maintained at this dose for an additional 7 days. Body weight, water consumption and assessment of CNS depression were obtained daily. Following the last day of pentobarbital infusion all rats were infused with saline for a 72-hour drug-free period. Water consumption, body weight and assessment of overt behavioral signs indicative of a drug withdrawal syndrome were obtained at specific times during the drug-free period. PB-5 rats showed little evidence of withdrawal while PB-20 rats demonstrated the greatest degree of withdrawal. Peak withdrawal scores were observed to be 1, 3.8 and 5 for PB-5, PB-13, and PB-20, respectively. Withdrawal scores for group PB-13 and PB-20 were found to be significantly greater than either control or PB-5 but were not significantly different from each other. Body weight for PB-13 and PB-20 mice declined slightly (nonsignificant) during the drug-free period while a significant decrease (40% decline) in water consumption was demonstrated by 24 hours of this period.(ABSTRACT TRUNCATED AT 250 WORDS)