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Hoffmeister F. 
“Negative Reinforcing Properties of Some Psychotropic Drugs in Drug-Naive Rhesus Monkeys”. 
J.Pharmacol.ExpTher.. 1975;192(2):468-77.
The negative reinforcing properties of some psychotropic drugs in drug-naive rhesus monkeys were investigated. Methods - : 8 Rhesus monkeys (2.5-5 kg) of either sex were implanted with jugular.vein catheters. Gold plate electrodes were placed s.c. in the head be-low ¿he major occipital nerve. To prevent tuberculosis the monkeys received lO mg/kg isoniazid-daily. The animals, . which had been previously trained to avoid electric shock, pressed a lever to put out a light associated with an i.v. drug infusion scheduled to begin 30 sec after the light had been switched on. Every response when the light was on put out the light for a l min time-out period (avoidance); The infusion was terminated by a response during the infusion (escape). The animals tolerated a large number of saline infusions under these conditions. Chlor - promazine (5.0-20 mcg/kg/infusion), LSD (1.0-2.5 mcg/kg/infusion) . or pentobarbital (l 0-t 00 mcg/kg/infusion) replaced saline each for 6 successive daily 2 be infusions.: Pentobarbital did not induce avoidance/escape-behavior during the extraction period, and was in fact tolerated better than saline infusions. The negative reinforcing effects of chlorpromazine occurred after a latent period of 3 days. During.the 1 st 3 days the animals tolerated all studied doses of chlorpromazine either to the same or greater extent than saline. During the and 3 days avoidance behavior was initiated leading to a dose-dependent decrease of tolerated infusions. The maximum effect was seen with infusions of l0 mcg/kg. LSD (0.5 mcg/kg/infusion) did not initiate avoidance behavior during both components of the 6 day replacement period. LSD (l mcg/kg/infusion) generated avoidance/escape behavior during the 2nd 3 days and ICED (2.5 ,mcg/kg/infusion) initiated avoidance/escape behavior beginning Ion the 1 st day of the replacement period. Chlorpromazine and LSD restored avoidance and escape behavior which had been extinguished in drug naive rhesus monkeys.
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