David A. Downs

Cocaine, d-Amphetamine, and Pentobarbital Effects on Responding Maintained by Food or Cocaine in Rhesus Monkeys

The effects of IM injections of cocaine, d-amphetamine, and pentobarbital were studied in rhesus monkeys whose lever-press responding was maintained under a second-order fixed-interval, fixed ratio schedule of reinforcement. Within each session, fixed-interval components, ending with the IV injection of 30 μg/kg cocaine (one group of monkeys) or the delivery of a 300 mg food pellet (second group of monkeys), alternated with fixed-interval components ending without an injection of cocaine or the delivery of food (extinction). Drug pretreatments generally caused comparable dose-related decreases in the overall rates of responding reinforced either by cocaine or by food. Response rates during extinction usually increased and then decreased as the dose of each drug increased. An analysis of the drug effects on response rates in different temporal segments of the fixed intervals showed that in both the reinforcement and extinction components, the normally low control rates of responding which occurred earlier in the intervals were usually increased, while higher control rates which occurred later in the intervals were increased less or decreased. Thus, the effects of these drugs were relatively independent of the reinforcing event (food or cocaine) and tended to depend more on the ongoing rate of responding under these conditions.

Behavioral functions of narcotic antagonists: response-drug contingencies.

Behavioral effects of the narcotic antagonist naloxone are discussed in terms of stimulus functions. As an eliciting stimulus, the effects of naloxone depend on prior administration of narcotic. Administered independently of responding, naloxone can increase or decrease rates of narcotic-reinforced responding depending on the dose of naloxone. When naloxone is administered as a consequence of narcotic self-injection, the further probability of that behavior is reduced; thus, naloxone can function as a punishing stimulus. As a negatively-reinforcing stimulus, naloxone can maintain behavior which terminates or prevents delivery in morphine-dependent monkeys. In animals with previous naloxone avoidance-escape experience, unavoidable-inescapable injection of naloxone produce increases in avoidance-escape response rates. In these animals, responding subsequently can be maintained, at least temporarily, when naloxone is administered only as the consequence of responding.

Food- and drug-reinforced responding: Effects of DITA and d -amphetamine

Intravenous pretreatment with DITA (0.1–1.0 mg/kg) decreased the rate of food-reinforced lever pressing in rhesus monkeys. Response rate decreases were dose-dependent but showed the development of tolerance. Self-administration of DITA was initiated and maintained in each of three monkeys when 30 lever presses were required to produce each injection. Maximal response rate during periods of drug availability was maintained by 0.03 mg/kg/injection while higher and lower doses (0.01 and 0.10 mg/kg/injection) maintained lower response rates. Response rate in periods of food availability immediately preceding drug periods was relatively constant across sessions; response rate in periods of food availability immediately following drug periods, however, decreased with increasing amounts of drug self-administered. Replication of initial self-administration doses produced results comparable to original determinations in contrast to the tolerance observed with DITA effects upon food-reinforced responding. DITA was about 3 times less potent than d-amphetamine in maintaining response rates in drug periods and in decreasing the rate of subsequent food-reinforced responding.