Cross-physical dependence liability of psychotropic drugs in rats dependent on barbiturates.

Rats were rendered physically dependent on phenobarbital by phenobarbital-admixed foods. Barbital, phenobarbital, ethanol, diazepam, nitrazepam, meprobamate, methaqualone, chlorpromazine, diphenylhydantoin, mephenesin, reserpine and clonidine were cross-administered to evaluate the mode of suppression of withdrawal signs and cross-physical dependence liability. The drugs were administered several times during the period from 17-18 hr (when withdrawal signs began to appear) to about 48 hr after the withdrawal of phenobarbital. From the mode of suppression and severity of relapsed withdrawal signs, these drugs were classified into the following 3 types: Type 1: drugs suppressing withdrawal signs of phenobarbital (WSP) almost completely and followed by the relapse of severe WSP. Type II-a: drugs suppressing WSP partially and followed by the relapse of moderate WSP. Type II-b: drugs suppressing WSP partially and followed by the relapse of only mild or practically no signs. Type III (III-a and -b): drugs practically failing to suppress or rather aggravate WSP. Consequently, we found that it was possible to evaluate precisely the cross-physical dependence on sedative-hypnotics by means of investigation for the method of suppression of WSP and the relapse of such signs upon their withdrawal.