Neuroregulators and the reinforcement of smoking: Towards a biobehavioral explanation

If the entire materia medica at our disposal were limited to the choice and use of only one drug, I am sure that a great many, if not the majority, of us would choose opium ([Macht, 1915][1]).

### A. Early History

Opium is the dried milky juice of the unripe seed capsule of the poppy, the Papaver

Opioids, Reward and Addiction: An Encounter of Biology, Psychology, and Medicine

Effect of environmental stressors on opiate and psychostimulant reinforcement, reinstatement and discrimination in rats: a review.

Six rhesus monkeys were trained to self-administer orally delivered phencyclidine (0.25 mg/mL) and saccharin (0.03% wt/vol) under concurrent fixed-ratio 16 schedules. In Condition 1 the fixed-ratio requirement for phencyclidine was changed from 16 to 4, 8, 16, 32, 64, 128 and 16 while the fixed-ratio requirement for saccharin deliveries remained constant at 16. In Condition 2 the fixed-ratio value for saccharin was systematically altered while the fixed-ratio requirement for phencyclidine remained at 16, and in Condition 3 the fixed-ratio requirements for both phencyclidine and saccharin were altered simultaneously. Water was then substituted for saccharin, and the series of fixed-ratio manipulations was replicated. The phencyclidine concentration was reduced to 0.125 mg/mL and Conditions 1 and 3 were repeated. When the fixed-ratio requirement for phencyclidine was increased and the fixed-ratio requirement for saccharin or water remained fixed at 16, phencyclidine deliveries decreased when saccharin (vs. water) was concurrently available. The magnitude of the decrease ranged from 20% to 90% (of the concurrent water condition) as the fixed-ratio requirement for phencyclidine increased from 4 to 128. When the fixed-ratio requirement for phencyclidine remained at 16 and the fixed-ratio requirements for concurrent saccharin or water varied between 4 and 128, phencyclidine deliveries decreased by 30% to 40% due to the concurrent availability of saccharin (vs. water). This decrease occurred only at the three lowest fixed-ratio values when saccharin intake was relatively high. When the fixed-ratio requirements for both phencyclidine and concurrent saccharin or water were varied simultaneously, phencyclidine deliveries were reduced from 20% to 45% when saccharin (vs. water) was concurrently present. There was little effect of reducing the phencyclidine concentration when the data were analyzed in terms of unit price (responses per milligram). Thus, changes in the fixed-ratio requirement or drug concentration were functionally similar, and unit price of phencyclidine was the variable that was influenced by the presence of concurrent saccharin. These data indicate that drug-reinforced behavior is substantially reduced when the environment is enriched with an alternative nondrug reinforcer. The economic context in which these substances are presented is an important determinant of drug-reinforced behavior.

Modifying drug-reinforced behavior by altering the economic conditions of the drug and a nondrug reinforcer.

The acceptability of nonmedical use for a particular drug is a function of diverse social needs. Drug dependence is due less to intrinsic effects than to the situation in which drug taking occurs. An addictive level of drug self-administration is a symptom of behavioral troubles rather than a definition of the trouble itself. The intrinsic effects of drugs do not in themselves produce either misuse or evoke specific kinds of behavior such as sexual or aggressive activities. Drugs can, however, come to function as discriminative stimuli for socially sanctioned behavior that would not under other circumstances be tolerated. The intrinsic reinforcing potential of an agent evolves in and dominates situations in which other reinforcing opportunities are either absent or remain unavailable to an individual who is unprepared to exploit them. While certain intrinsic properties of a drug contribute to its potential as a reinforcer (e.g., rapid onset and brief duration of action), reinforcing efficacy is notoriously malleable. It is a function of historic and currently-acting factors, particularly social reinforcers. The importance of physical dependence in the maintenance of drug seeking and taking is mainly unproven and probably overrated. Situations under which important reinforcers are available only in small portions intermittently can induce various excessive activities, including an untoward concern with obtaining and using drugs. Drug dependence prevention as a species of environmental dependence can be best effected by either alterations in the intermittent reinforcement situations inducing excessive behavior or by providing opportunities and training with respect to reinforcing alternatives other than drugs.

Drug dependence: myth or motive?

Experiment 1 reported the effects of the interaction of a fixed 1 min delivery schedule and body weight, using schedule-induced self-injection paradigm, in the rate of acquisition of methadone and heroin. Eighty-one rats were assigned to 100% and 80% reduced body weight conditions with and without a schedule. The findings show that: (a) voluntary heroin and methadone intake was enhanced when a schedule was introduced to animals at 80% but not at 100% body weight; (b) high intake of heroin and methadone was accompanied by increased levels of plasma 11-OHCS. Experiment 2 showed that the high rate of self-injection was due to the interaction of pharmacological properties of opiates and environmetal variables rather than to a general increase in activity arising from the deprivation state or the effects of the schedule. The results are discussed in terms of a stress factor arising from an interaction between environmental and pharmacological factors.

D. Jefferys

Papers

The interaction of a fixed time food delivery schedule and body weight on self-administration of narcotic analgesics

A reconsideration of the concept of drug dependence