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PubMed1986

Temporal patterns of reinforcer-induced general activity and attack in pigeons.

Three White King pigeons were exposed to fixed-time schedules ranging from 60 to 240 sec. General activity and attack against a conspecific target were measured separately at each interreinforcer interval value. Comparison of the temporal distributions of activity and attack revealed significant differences in their temporal locus and overall distribution between reinforcer presentations. At all interval values, attack was localized to the postreinforcer period, and peaked at the same absolute time (5-10 sec) following each reinforcer presentation. General activity was more uniformly distributed between reinforcers, and the peak level occurred later in the interval. As the interval length increased, peak levels of activity shifted to later times following reinforcement. These differences question traditional accounts which posit a unitary process underlying induced behaviors, while supporting Cohen, Looney, Campagnoni and Lawler's recent two-state model of induced behaviors.

Aggression↗
PubMed1991

Influence of neurotransplantation on rats' behavior with different conditions of reinforcement.

Recently, we have reported a marked rat lateralization in the T-maze choice. Embryonic rat tissue from neocortex, hippocampus, hypothalamus and amygdala was transplanted into intact rat brains in various combinations: 1) neocortex and hypothalamus (Neo + Hyp); 2) hippocampus and amygdala (Hipp + Amyg); 3) neocortex and hippocampus (Neo + Hipp); and 4) hypothalamus and amygdala (Hyp + Amyg). Once under conditions in which reinforcement was equally qualitative and equally probable, rats in all groups chose the T-maze arm contralateral to the side of implantation. In a second set of experiments, rats were presented a choice between quality and probability of reinforcement. The right arm of the T-maze contained a cup of water 33% of the time (high-quality but low-probability reinforcement). The left sleeve contained a solution of 0.15% quinine in water 100% of the time (low quality but high probability of reinforcement). Rats that received Neo + Hyp transplants chose the T-maze arm that always contained a drink cup with water significantly more often than they chose the arm that always contained the drink cup with quinine solution. Rats that received Hipp + Amyg transplants chose the arm containing the drink cup with quinine solution much more often than the arm that sometimes contained a cup of water. Rats with transplanted Neo + Hyp generally were more active than rats with transplanted Hipp + Amyg. These data suggest that the behavior of rats can be affected by selective transplantation of different brain tissue.

Amygdala↗
PubMed1993

The effects of atrial natriuretic peptide on food-reinforced conditioning in rats. Interactions with neurotransmitters.

The effects of two doses of rat atrial natriuretic peptide (TANP-1-28), 200 and 500 ng, on 6-day acquisition and extinction of food-reinforced conditional learning (conditional stimulus: light) were studied in rats following administration into the lateral cerebroventricle. With the higher dose, there was a tendency for facilitated acquisition and significantly delayed extinction of the positively reinforced learning task. In order to clarify whether the effect of the peptide is obtained through the involvement of neurotransmitters, the experimental animals were pretreated with different receptor blockers in selected doses that did not influence the behavioral test. Haloperidol, atropine, phenoxybenzamine, and propranolol blocked the action of ANP on extinction of the food-reinforced conditioning, whereas naloxone, bicuculline, and methysergide were ineffective. The results suggest that ANP might be considered a modulating agent in a positively reinforced conditional learning task, and that its action might involve dopaminergic, cholinergic, and alpha- and beta-adrenergic mechanisms.

Animals↗
PubMed1976

The role of reinforcement loss in tolerance to chronic delta9-tetrahydrocannabinol effects on operant behavior of rhesus monkeys.

Two monkeys were trained on a multiple fixed-interval (FI) 120 sec, differential reinforcement of low rate (DRL) 120 sec schedule of food reinforcement for lever pressing in which the two schedules, each correlated with a distinctive cue, alternated throughout an experimental session. Under chronic daily treatment with delta-9-tetrahydrocannabinol in a dose of 7 mg per os (1 mg/kg), for 40 consecutive days, responding increased in both schedules. Performance on the DRL schedule was affected less dramtically than that on the FI schedule. Even though reinforcement frequency on the DRL schedule remained suppressed and FI reinforcement frequency was unaffected during chronic drug treatment, DRL performance showed greater tolerance than FI performance.

Animals↗
PubMed1977

Effects of schedules of reinforcement on brain catecholamine metabolism in the rat.

Rats were trained on a fixed ratio 5 (FR 5) for 0.01 ml water reinforcer, a fixed ratio 20 (FR' 20) for 0.01 ml water reinforcer, a fixed ratio 20 (FR 20) for 0.04 ml water reinforcer, a variable time 15 sec (VT 15 sec) for 0.01 ml water reinforcer, a variable time 30 sec (VT 30 sec) for 0.01 ml water, variable time 60 sec (VT 60 sec) for 0.01 ml water, or a variable time 60 sec (VT 60 sec) for 0.10 ml water. In all these schedules, the rate of NE metabolism varied with the number of water presentations but not with the number of responses or the volume of water. The rate of metabolism of DA was increased over control values in rats on the VT schedules but no significant differences could be found in DA metabolism among the rats performing on the various VT schedules or receiving various volumes.

Animals↗
PubMed1978

Cocaine reinforced progressive ratio performance in the rhesus monkey.

A series of experiments were conducted to determine the effectiveness of a progressive ratio (PR) procedure in measuring the relative reinforcing efficacy of several intravenous doses of cocaine. In Experiment 1, utilizing much smaller increases in the ratio requirement than previously reported, the animals generally displayed increases in breaking point with increases in the cocaine unit dose up to 0.4 mg/kg/inj. The highest dose studied (0.8 mg/kg/inj.) engendered breaking points lower than the 0.4 mg/kg dose but higher than the remaining lower doses. Experiment 2 was conducted utilizing the same reinforcement schedule as in Experiment 1 but with liquid Tang as the reward. The results demonstrated that this procedure would function to discriminate reinforcing strength with a more traditional reward. Experiment 3 examined a more expedient procedure to see if results similar to those seen in Experiment 1 could be obtained in a shorter period of time. However, the shorter procedure engendered excessive intrasubject variability, suggesting that some intermediate level of baseline experience between the 5-7 days used in Experiment 1 and the 50 reinforced responses used in Experiment 3 would be necessary to obtain consistent breaking point-unit dose functions.

Animals↗
PubMed1978

Pipradrol enhances reinforcing properties of stimuli paired with brain stimulation.

The hypothesis that a psychomotor stimulant drug (pipradrol) enhances the reinforcing effects of stimuli paired with reinforcing brain stimulation was tested using a conditioned reinforcement paradigm. Rats were trained to discriminate between two stimuli (S+ and S-) to obtain ICS in the lateral hypothalamus by pushing a panel in the presence of S+. In a subsequent preference test, ICS was no longer available, but responding on one of two novel levers now produced S+, whereas responding on the other lever produced S-. Four groups of four rats received 0, 5, 10 or 15 mg/kg pipradrol. Doses of 5 and 10 mg/kg significantly enhanced the preference for S+ over S-. These doses increased responding for S+, but had no effect on responding for S-. These results support the hypothesis tested, and suggest that pipradrol potentiates the effects of conditioned reinforcement.

Animals↗
PubMed1978

Effects of methadone on behavior maintained by fixed ratio reinforcement schedules.

The effects of subcutaneous injections of methadone hydrochloride (0.75mg, 1.5mg and 2.5mg/kg) on lever pressing maintained by fixed ratio schedules of reinforcement were examined in C57BL/6J and DBA/2J mice. Response output over a 30 min session decreased as a function of increasing drug dose when reinforcement was delivered for every 5 responses. Increasing the response to reinforcement ratio from 5 to 20 in a second experiment doubled and nearly quadrupled responding by DBA and C57 mice, respectively. Injecting animals maintained on this schedule with methadone reduced responding to the same extent as that observed in the first experiment when response rates were lower. Hence, these experiments provide no support for the effect of methadone being rate-dependent. In both experiments methadone disrupted responding of DBA more than that of C57 mice. This finding is consistent with a previous report that other narcotic analgesics were more potent analgesics for DBA than for C57 mice. From these studies it appears that the opposite changes in locomotor activity upon an exposure to narcotic analgesics does not generalize to behavior under control of reinforcing stimuli; and that both the effects obtained in the present study and the analgesic action are dissociated from the effects of these drugs on locomotor activity.

Animals↗
PubMed1979

Reinforcement with intragastric infusions of ethanol: blocking effect of FLA 57.

Suppression of oral intake of ethanol by FLA 57 has been reported for rats and was attributed to an inhibition of dopamine beta-hydroxylase. We have demonstrated the ability of FLA 57 (50 mg/kg, IP) to suppress bar-pressing for intragastric (IG) delivery of doses of ethanol (25 mg/kg). This indicates that the effect on oral intake of ethanol may not be attributed to a taste factor, e.g., a decreased palatability of the ethanol solution. The same dose of FLA 57 did not suppress responding for IG doses of sweet milk. Thus, there was not an impairment of appetitive behavior in general through some nonspecific depressant or toxic action. Furthermore, the primary reinforcing action of ethanol, when used to establish a buzzer as a conditioned reinforcer through repeated pairings, was blocked if FLA 57 was given before pairings. This was evidenced by a failure of such rats to bar-press above the baseline level in a later test of conditioned reinforcement, which contrasted with the increased responding seen for rats receiving saline instead of FLA 57 before ethanol. These data support the previous findings on oral ethanol and confirm that FLA 57 can impair the mechanism by which ethanol produces positive reinforcement in rats.

Animals↗
PubMed1979

Reinforcing properties of some local anesthetics in rhesus monkeys.

The reinforcing properties of several local anesthetics were determined in rhesus monkeys experienced in the intravenous self-injection of cocaine. Intravenous procaine and, occasionally, tetracaine maintained response rates higher than did vehicle injections in most monkeys. In contrast, lidocaine, procainamide and diethylaminoethanol (a metabolite of procaine) failed to maintain responding resulting in their intravenous delivery. These results demonstrate that not all local anesthetics are positive reinforcers in the rhesus monkey when delivered intravenously. Furthermore, the reinforcing properties of procaine probably cannot be attributed to its metabolite diethylaminoethanol. The data suggest that short-acting, esteratic local anesthetics are most likely to have reinforcing properties in the rhesus monkey.

Anesthetics, Local↗
PubMed1980

Reinforcing effects of morphine microinjection into the ventral tegmental area.

A neural substrate for the reinforcing property of an opiate drug was identified in the ventral tegmental area (VTA) by establishing conditioned reinforcement to salient environmental stimuli paired with intracerebral microinjections of morphine. Bilateral microinjections of morphine into the VTA in doses of 0.2 microgram and 1.0 microgram produced a subsequent change in place preference to a distinctive compartment previously associated with the stimulant effects of morphine. Microinjection of 1.0 microgram morphine at sites 2.5 mm dorsal to the VTA had no effect. Pretreatment with naloxone (2 mg/kg) antagonized the reinforcing effects of 1.0 microgram morphine as this group showed no significant change in place preference. Nor did control groups receiving microinjections of sterile physiological saline. Taken together, these data suggest that opiate receptors, located in the ventral tegmental area, play an important role in mediating the reinforcing effects of morphine. The possible involvement of dopaminergic neurons in these effects is discussed.

Animals↗
PubMed1983

Rate-dependent effects of amphetamine on responding under random-interval schedules of reinforcement in the rat.

The parameters of 12 random-interval schedules (cycle length and interreinforcement interval) were varied systematically in order to examine the ability of these schedules to separate the usual relationship between response rate and reinforcement frequency using rats. Response rates varied over a two-fold range for the same frequency of reinforcement under random-interval 30-sec schedules. However, cycle length did not alter response rates significantly at other interreinforcement intervals. Subsequently, the effects of amphetamine on random-interval responding were examined in order to evaluate the roles of control rates of responding and reinforcement in amphetamine's actions. Amphetamine's effects were significantly correlated with both control response rate and control rate of reinforcement. However, by comparison, control response rate was the better predictor of amphetamine behavioral effects. The results support the rate dependency hypothesis that control rate of responding is closely associated with amphetamine's effects on operant behavior.

Animals↗
PubMed1986

Reinforcing and phencyclidine-like stimulus properties of enantiomers of metazocine.

The positive reinforcing properties of the racemate and stereoisomers of the benzomorphan, metazocine, were tested in three rhesus monkeys trained to self-administer IV injections of cocaine. The (-)-isomer maintained responding above saline levels at the highest dose tested (30 micrograms/kg/injection) in two of the three monkeys. Likewise, (+)-metazocine maintained self-administration responding in two monkeys at a dose of 100 micrograms/kg/injection. Responding for (+-)-metazocine was maintained in all three monkeys at doses of 10-100 micrograms/kg/injection. The discriminative stimulus properties of the three forms of metazocine were tested in rats trained to discriminate phencyclidine (PCP; 3.0 mg/kg) from saline on a two-lever food-reinforced operant task. When metazocine was tested in these animals, only the (+)-isomer produced dose-related increases in responding on the PCP-lever. Both (+-)- and (-)-metazocine resulted in only saline-appropriate responding. Thus, the results of these two experiments demonstrate that both enantiomers of metazocine function as positive reinforcers in monkeys and further, the reinforcing properties of (+)-metazocine may be due to the PCP/sigma properties of this isomer.

Animals↗
PubMed1986

Genetic differences in the establishment of ethanol as a reinforcer.

Ethanol, self-administered orally, has been shown to serve as an effective reinforcer in several species. Self-administration studies have also illustrated that ethanol-drinking behavior can be conceptualized as a specific type of operant behavior. The use of inbred and selectively bred animals in other areas of alcohol research has provided valuable information about the contribution of genetic factors to ethanol-related behaviors. Our research was designed to study genetic differences in oral self-administration in the ALKO AA (Alcohol Accepting) and ANA (Alcohol Non-Accepting) rat lines, selected for ethanol preference. Thus, we applied a behavior genetic analysis to aid in determining the contribution of genetic factors to behavior, specifically drug-seeking behavior. The results of our experiments indicate that genetic differences are important factors contributing to the establishment of a drug as a reinforcer. At least in the case of ethanol, the drug did not act as a reinforcer in non-preferring animals. Conversely, in preferring animals, ethanol was readily established as a reinforcer.

Alcohol Drinking↗
PubMed1989

Effects of corticotropin releasing factor, desipramine and haloperidol on a DRL schedule of reinforcement.

Rats were trained on a schedule of differential-reinforcement-of-low-rate (DRL) which has been proposed to be differentially sensitive to antidepressant drugs. Desipramine and haloperidol decreased response rate and increased reinforcement rate. CRF decreased response rate and failed to change reinforcement rate. Amphetamine produced the opposite pattern of increased response rate and decreased reinforcement rate. These results question the specificity of the DRL task as a screen for antidepressants and suggest that drugs that moderately lower response rate may produce a behavioral profile on this task similar to that of tricyclic antidepressants.

Amphetamine↗
PubMed1989

Breaking points on a progressive ratio schedule reinforced by intravenous apomorphine increase daily following 6-hydroxydopamine lesions of the nucleus accumbens.

It has been shown previously that 6-hydroxydopamine (6-OHDA)-induced lesions of the nucleus accumbens cause extinction of cocaine self-administration behavior, yet fail to affect the rate of apomorphine self-administration on a Fixed Ratio 1 schedule of reinforcement. Since the dopamine (DA) receptors in this nucleus should become supersensitive, and since these receptors are thought to mediate the reinforcing effects of apomorphine, then some change in apomorphine self-administration would be expected. We have therefore reinvestigated the effect of 6-OHDA lesions on apomorphine self-administration using a progressive ratio schedule of reinforcement. Rats were trained to self-administer apomorphine (0.033 mg/inj, IV) on a schedule in which the response requirements increased after each reinforcement. The breaking point was defined as the final ratio completed during each daily session. Sham lesions had no effect on the breaking points, and a steady increase in the breaking point was observed in the 6-OHDA-lesioned animals which may parallel the development of DA receptor supersensitivity.

Animals↗
PubMed1989

The effects of amphetamine on a multitrial partial reinforcement extinction effect (PREE) in an operant chamber.

Two experiments investigated the effects of d-amphetamine (1 mg/kg) on the partial reinforcement extinction effect (PREE) in an operant chamber using a discrete multitrial procedure. Experiment 1 used a random 50% partial reinforcement (PRF) schedule. Experiment 2 used two 40% PRF schedules: one schedule maximized the number of nonreinforced trials preceding any given reinforced trial (maximum N-length of four) and the second maximized the number of N-R transitions (N-length of one). In both experiments, the continuously reinforced (CRF) animals received a reward on every trial. The PREE, i.e., increased resistance to extinction of PRF as compared to CRF animals, was obtained in the random 50% PRF and the schedule maximizing N-length in both the placebo and amphetamine-treated animals. Both drug and no-drug animals failed to exhibit PREE on the schedule maximizing N-R transitions. These results show that on a PRF schedule with short intertrial intervals, amphetamine-treated animals are not impaired in their capacity to learn sequences of events and to associate the outcomes of preceding trials with subsequent consequences.

Amphetamine↗
PubMed1995

Oral self-administration of etonitazene in rhesus monkeys: use of a fading procedure to establish etonitazene as a reinforcer.

The establishment of orally delivered etonitazene (a potent opioid) as a reinforcer, was studied in eight rhesus monkeys. Initially, when given concurrent access to 2.5 micrograms/ml etonitazene and the water vehicle, five of the monkeys rejected the drug, whereas the other three monkeys consumed more drug solution than water. The five monkeys that rejected the drug solution underwent an acquisition phase to establish the drug as a reinforcer. A fading procedure was used to transfer control of responding from a 2% (wt/vol) ethanol solution to a 2.5 micrograms/ml etonitazene solution. Initially, responding was maintained by contingent deliveries of 2% ethanol. Next, across blocks of six or more sessions, increasing amounts of etonitazene were added in steps to the 2% ethanol solution. Subsequently, the 2% ethanol solution was decreased in steps to zero, leaving only the 2.5 micrograms/ml etonitazene present. When the fading procedure was completed, dose of etonitazene was varied by increasing the volume delivered, first under fixed ratio (FR 4) and then under an FR 8 reinforcement schedule. The same dose manipulations were made with the three monkeys who did not undergo the fading procedure because they preferred etonitazene over water when first tested. Etonitazene was established as a reinforcer for six of the eight monkeys because drug deliveries exceeded vehicle deliveries across a range of drug doses.

Administration, Oral↗