Evaluation of nefazodone self-administration in rhesus monkeys.
Intravenous self-administration of nefazodone, a potential new antidepressant medication, was evaluated using a substitution procedure in rhesus monkeys. Subjects had established stable rates of responding for cocaine (0.033 mg/kg per infusion) under a fixed-ratio 10 schedule during 60-min sessions each day. Various does of nefazodone hydrochloride (0.03-0.3 mg/kg per infusion) were substituted for cocaine for four consecutive daily self-administration sessions. Compared to rates of responding obtained during saline substitutions, nefazodone failed to function as a reinforcer when substituted for cocaine. In only one monkey, at one dose, did the rate of responding exceed the range of saline responding; an effect not observed in two subsequent replications in that subject. In all three monkeys, the total number of infusions tended to decrease during the 4-day nefazodone substitution and the majority of nefazodone infusions occurred during the first quarter of each session, with few infusions occurring in the latter three-quarters. Overall intake of nefazodone increased as a function of dose per infusion. Such a result is expected when response rates do not vary with dose, which is more likely to occur when a test drug is not a reinforcer. In summary, the present results provide no evidence of reinforcing effects with nefazodone and suggest that it would possess little or no abuse liability.
Gold
L H
LH
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613.
Balster
R L
RL
D000818:Animals; D001143:Arousal / Q000187:drug effects; D003042:Cocaine; D007262:Infusions, Intravenous; D008253:Macaca mulatta; D008297:Male; D010879:Piperazines; D012054:Reinforcement, Psychology; D012646:Self Administration / Q000523:psychology; D019966:Substance-Related Disorders / Q000523:psychology*; D014230:Triazoles / Q000008:administration & dosage*
D010879:Piperazines; D014230:Triazoles; C051752:nefazodone; D003042:Cocaine