Orally-delivered methohexital was demonstrated to function as a reinforcer for rhesus monkeys with either phencyclidine or pentobarbital self-administration histories. The effects of food deprivation and food satiation were compared across a wide range of methohexital concentrations. Initially, three monkeys were trained to orally self-administer phenyclidine (0.25 mg/ml) and water, and three were trained to orally self-administer pentobarbital (0.5 mg/ml) and water under concurrent fixed-ratio (FR) schedules during daily 3-hr sessions. Liquid deliveries during the session (drug and water) and intersession (water) were contingent upon lip contact responses on solenoid-operated drinking spouts. The monkeys were first tested while food deprived by maintaining them at 85% of their free-feeding body weights. Methohexital concentrations were presented in the following order, and each concentration was held constant until at least five or six sessions of stable behavior were obtained: 2, 2.8, 4, 2 (retest), 1, 0.5, (plus 0.25 and 0.125 in monkey M-W) and 2 (retest) mg/ml. The monkeys were then food satiated by allowing them unlimited access to food, and the methohexital concentration series was repeated. During food deprivation, the concentration-response functions generally resembled an inverted U. Concurrent water-maintained responding was generally low, but it increased in some monkeys as methohexital concentrations increased in some monkeys. During food satiation, methohexital-maintained responding was not different from water-maintained responding in some monkeys, but in others it was substantially higher than water-maintained responding. Maximum drug intake ranged from 20.4 to 93.8 mg/kg during food deprivation and from 6.4 to 64.2 during food satiation among the six monkeys. During food deprivation, most methohexital-maintained responding occured during the first half of the 3-hr session; however, during food satiation, responding was evenly distributed throughout the 3-hr session. The time course of water-maintained responding was not altered as a result of changes in the feeding condition. Generally it appeared that methohexital was more easily substituted for pentobarbital than it was for phencyclidine, and higher rates of performance were maintained in the pentobarbital-trained monkeys.
Bibliographical noteFunding Information:
We thank Greg Lemaire. Kathy Manion, Heidi Noetzel, Jim Pederson, David Sauter, Ignatius Tan and Jane Wright for their technical assistance and G.L. and I.T.'s critical comments on the manuscript. The gift of methohexital from the Lilly Research Laboratories is greatly appreciated. This research was supported by NIDA grants DA 02486 and 03240 to M.E.C. and a NIDA grant DA 00944 and a Research Scientist Development Award (DA 00007) to R.A.M.
- Drug history
- Food deprivation
- Food satiation
- Lip-contact response
- Oral drug self-administration
- Rhesus monkeys