Reinforcing properties of clonidine in rhesus monkeys

Intravenous clonidine self-administration was studied in rhesus monkeys under conditions of limited and unlimited access. Limited access consisted of daily 2-h experimental sessions with drug available on a fixed ratio 10 schedule. For unlimited access, drug was available 23 h/day with each response resulting in an injection. In all animals under both conditions, responding was maintained at levels that were above those maintained by saline injections at doses between 0.3 and 10 microgram/kg/inj, and the number of injections taken per session depended upon the dose. Under conditions of limited access, peak self-administration rates varied between animals but averaged approximately 30 inj/session. Total session intake was occasionally in excess of 1.0 mg/kg. Under conditions of unlimited access animals frequently self-administered more than 300 inj/day and intakes averaging 3.6 mg/kg/day occurred at the highest dose tested (10 microgram/kg/inj). When saline was substituted for clonidine after periods of clonidine access that ranged from 10-40 days, withdrawal signs included facial flushing, refusal of preferred food, restlessness, salivation, and emesis. These signs could be reversed with IV clonidine but could not be reliably precipitated with IV naloxone.