Self-injection of barbiturates, benzodiazepines and other sedative-anxiolytics in baboons.
Self-injection of 12 sedative-anxiolytics was examined in baboons. Intravenous injections and initiation of a 3-h time-out were dependent upon completion of a fixed-ratio schedule requirement, permitting eight injections per day. Before testing each dose of drug, self-injection performance was established with cocaine. Subsequently, a test dose was substituted for cocaine. At some doses, all five of the benzodiazepines examined (alprazolam, bromazepam, chlordiazepoxide, lorazepam, triazolam) maintained rates (number of injections per day) of drug self-injection above vehicle control in each of the baboons tested. Maximum rates of benzodiazepine self-injection were generally submaximal. Of the benzodiazepines examined, triazolam maintained the highest rates of self-injection. Among the three barbiturates tested, methohexital generally maintained high rates of self-injection in contrast to hexobarbital and phenobarbital, which only maintained low rates. Of the four non-benzodiazepine non-barbiturate sedatives examined, both chloral hydrate and methyprylon occasionally maintained high rates of self-injection. Although there were differences within and across animals, baclofen maintained intermediate rates of self-injection. The novel anxiolytic buspirone maintained only low rates of self-injection that were not different from vehicle. This study further validates the self-injection methodology for assessing sedative-anxiolytic abuse liability and provides new information about drug elimination rate as a determinant of drug self-administration.
Griffiths
R R
RR
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Lamb
R J
RJ
Sannerud
C A
CA
Ator
N A
NA
Brady
J V
JV
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001463:Barbiturates / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines; D003042:Cocaine / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects; D006799:Housing, Animal; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D010215:Papio; D012055:Reinforcement Schedule; D012646:Self Administration
D014151:Anti-Anxiety Agents; D001463:Barbiturates; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; D003042:Cocaine