Orcadian Manifestations of Barbiturate Habituation, Addiction and Withdrawal in the Rat

Abstract

The thermal acrophase for the circadian oscillation of core temperature in Charles River male rats fed ad libitum and entrained by light (12 hr dim light and 12 hr bright light) (DL12: 12 hr) occurred near the middle of the dim phase on a control diet of 30+ protein. Dietary phenobarbital (0.25+) caused an increase in amplitude of the oscillation (from 0.7° to 1.2°C) and a phase-angle difference (ψ-advance) between the zeitgeber and the biological oscillation of about 32°, equivalent to an advance in the thermal acrophase of 2.1 hr in the steady-state. Food consumption was monitored continually and was nearly the same in the two groups; however, animals on the control diet ate around the clock, albeit at a greater rate during dim light than during the bright light phase, whereas rats on phenobarbital started to eat earlier and confined their feeding almost exclusively to early dim phase. This pattern of increase in amplitude of the thermal oscillation and of feeding closely resembling programmed feeding, persisted in phenobarbital-treated animals even in the absence of a dim light-bright light (DL) zeitgeber for eight days. Similar behavior was seen in rats entrained by illumination cycles of 17 hr of dim light and 7 hr of bright light, but with this reduced phase ratio for the zeitgeber, few (ψ-shifts occurred, and these were smaller than those induced in the group receiving 12 hr of dim light and 12 hr of bright light. In each group, introduction of the drug into the diet and, even more noticeably, removal of the drug from the diet, induced transients of circadian dyschronism that persisted for 4–5 days.

Key Words:

• Barbiturate
• addiction
• tolerance
• phenobarbital
• habituation
• withdrawal
• circadian