Larry D. Reid

Affective states associated with morphine injections

Rats were placed in one compartment of an alley for 30 min at 1, 4.5, and 7 h after morphine (10 mg/kg) or saline injections on 3 consecutive days. On the 4th day, rats were allowed access to the entire alley while time spent in the compartment where they had experienced the effects following injections was tabulated. This 4-day cycle of training and testing was repeated four times. Additionally, other rats were trained and tested at 4.5 h after injections for the first cycle and decreased to 2 h for the fourth cycle, times corresponding to morphine’s maximum facilitation of hypothalamic self-stimulation. On test days, rats experiencing morphine in a compartment during times corresponding to morphine’s facilitation of self-stimulation, and at 1 h after injections, spent more time in that compartment than rats experiencing saline.

Addictive agents and intracranial stimulation: Daily morphine and lateral hypothalamic self-stimulation

Rats were allowed to press for electrical stimulation of the lateral hypothalamus on days before, during, and after daily morphine or placebo injections. During tests 1 h after morphine injections, press rates were initially depressed at doses of 10 mg/kg or greater. As days of testing under daily morphine doses of 10 or 15 mg/kg continued, pressing gradually increased 1 h after injections. Four hours after morphine injections with doses of 10 and 15 mg/kg, pressing rates were greater than rats’ previous rates of pressing and control groups’ pressing, and this facilitation did not wane across 20 days of injections. With termination of 20 days of injections, pressing rates generally returned to levels seen prior to days of injections. The facilitation of intracranial self-stimulation at 4 h after injections of moderate doses of morphine might reflect processes germane to morphine’s positively reinforcing properties.

Morphine injections in the taste aversion paradigm.

In three separate studies, rats were presented with a flavored solution and then injected with one of a variety of doses of morphine in the taste aversion paradigm. Presentations of the flavored water and injections were done 17 times in one study. Doses of from 2 to 20 mg/kg of morphine were sufficient to suppress drinking of the flavored solution and the extent of the suppression was hardly modified across continuous injections. Furthermore, in one experiment it was demonstrated that injections following the first five injections still had capabilities of suppressing drinking. It made little difference whether the injections were subcutaneously or intraperitoneally given. There were considerable individual differences with respect to extent of suppression of drinking the flavored solution. Some rats showed almost complete suppression but others only a slight suppression.

Suppression of running times by olfactory stimuli

Thirsty rats running a straight-way for water were exposed to the odor of rats which had received foot-shock, a perfumed spray deodorant, and the essence of cat. Running times of Ss increased when they first encountered each of the odors. The odor of cat was particularly effective in suppressing Ss’ approach. The first encounter with the odors seemed to function as a mild punishment. Control for odors such as those left by rats which have received foot-shock may be important in many experimental situations.

Addictive agents and intracranial stimulation (ICS): Daily morphine and pressing for combinations of positive and negative ICS

Ten rats were fixed with two chronically indwelling bipolar electrodes, stimulation of one producing positive intracranial stimulation (P-ICS) and stimulation of the other producing aversive, or negative, intracranial stimulation (N-ICS). Subjects pressed a lever daily for P-ICS and for combinations of P-ICS and N-ICS. Following baseline measurements, five rats received daily injections of morphine sulfate (15 mg/kg, 4 h before testing) for 20 days while the other five received placebos. Press rates of the morphine subjects for P-ICS increased about 20% from baseline rates and from rates of rats under placebo some days after injections were begun, and these increases were then maintained throughout the days of injections. For the combined P-ICS and N-ICS, press rates of rats of morphine decreased with continued injections. Because of morphine’s differential effects on pressing for P-ICS and on pressing for combinations of P-ICS and N-ICS, it is suggested that morphine’s facilitatory effect on hypothalamic self-stimulation is not related to its analgesic properties.

Addictive agents and intracranial stimulation: Morphine and thresholds for positive intracranial reinforcement

Rats were fixed with chronically indwelling bipolar electrodes. Subsequently, they pressed for direct electrical stimulation of the lateral hypothalamus. Then thresholds for the positive intracranial reinforcement were measured daily for 20 days while rats were under the influence of morphine injections (10 mg/Kg given 3.5 h prior to testing). Morphine reduced thresholds after the first few days of dosing and the reductions, once seen, did not wane with further dosing. Furthermore, thresholds were reduced by a 10-mg/kg dose of morphine following a regimen of dosing with morphine that produced physical dependence. It was concluded that morphine reduced thresholds for positive intracranial reinforcement and this capability was not changed by assimilation of relatively large quantities of morphine, that is, the effect did not show tolerance.

Morphine injections in the taste aversion paradigm: Extent of aversions and readiness to consume sweetened morphine solutions

In three experiments, groups of rats were subjected to the procedures of classical taste aversion testing using morphine injections as the unconditioned stimulus. Subsequently, rats’ consumption of sweetened morphine solutions was tabulated. In both tests of taste aversion and of readiness to consume sweetened morphine solutions, there were marked individual differences in rats’ reactivity. The extent to which rats drank the flavored solution that had previously been paired with morphine injections was related to initial tendencies to consume sweetened morphine solutions. Extent of taste aversions established with lithium chloride, in a dose known to be poisonous, was greater than extent of aversions established with morphine. Extent of aversions following lithium injections was not related to consumption of morphine solutions. Rats’ readiness to consume morphine solutions is probably related to initial negative consequences that may accompany assimilation of morphine.

Methods of deconditioning persisting avoidance: Drugs as adjuncts to response prevention

Rats were trained, across 3 daily sessions, to avoid intense footshock in an automated one-way avoidance box. Subsequent to training and termination of footshock, groups of rats received different treatments, and all were tested for persistence of avoidance 3 days later. One group’s treatment was only handling, a no-treatment group. All other groups were given response prevention, i.e., 10 min on the previously shocking grid without the opportunity to avoid. Groups of rats experienced response prevention under the influence of saline or doses of drugs: meprobamate, meprobamate in conjunction with atropine, atropine alone, atropine methyl nitrate, physostigmine, ethanol, morphine sulfate, amphetamine, chlordiazepoxide, and chlorpromazine. Only atropine led to reliably less persisting avoidance than response prevention controls, whereas doses of chlordiazepoxide led to more persisting avoidance. These data provide little support for the idea that widely used “psychotropic” drugs are effective in aiding the reduction of anxiety-fear-avoidance when postdrug behavior is the criterion for a drug’s effectiveness.

Methods of deconditioning persisting avoidance: Response prevention and counterconditioning after extensive training

Rats were fixed with a chronically indwelling electrode for intracranial stimulation (ICS) of a site of stimulation that elicited positive affect. After recovery from surgery, each rat was forced to avoid or escape footshock for 100 trials/day for 10 days in an automated one-way avoidance chamber. After 1,000 trials, footshock was discontinued and trials measured to extinction. Between shock discontinuance and extinction trials, one group received time on the grid with the ledge removed, a response prevention treatment. Another group spent the same time in response prevention and also received periodic ICS, a counterconditioning treatment. A third group spent time outside the chamber, a no-treatment control. The group of counterconditioning responded reliably less during extinction. These data confirm the conclusion drawn from similar studies using only limited avoidance training that counterconditioning is a superior treatment for reducing persisting avoidance.

Methods of deconditioning persisting avoidance: Amphetamine, chlorpromazine, and chlordiazepoxide as adjuncts to response prevention

Rats were given extended avoidance training in an automated one-way avoidance chamber, a chamber with a retractable ledge. After training and footshock termination, some rats were prevented from responding by being trapped on the footshock grid with the ledge removed. During this response prevention, rats were under the influence of either amphetamine, chlorpromazine, cnlordiazepoxide, or a placebo. Subsequently, rats were tested for continuance of responding when footshock no longer occurred. Only response prevention with amphetamine reduced persisting avoidance responding compared to no treatment.