Punished behavior: increases in responding after d-amphetamine

Responding maintained in squirrel monkeys under a 10-min fixed-interval schedule of food presentation was suppressed by presenting a shock after every 30th response (punishment). During alternate 10-min periods of the same experimental session, but in the presence of a different discriminative stimulus, responding either had no effect (extinction) or postponed delivery of an electric shock (avoidance). During sessions when the avoidance schedule was not in effect, d-amphetamine sulfate decreased punished responding. When the avoidance schedule was present during alternate 10-min periods, however, d-amphetamine (0.01 minus 0.56 mg/kg, i.m.) markedly increased responding during punishment components. Increases in responding during avoidance components were also evident. The effects of d-amphetamine on punished responding depend on the context in which that responding occurs.     

Relaxation measured by EMG as a function of vibrotactile stimulation

Key pecking of two pigeons was maintained under a multiple schedule of food presentation. In the presence of one keylight stimulus responding produced food according to a fixed-interval 5-min schedule. Additionally, during this component, each 50th response produced electric shock. When a different keylight stimulus was present, key pecking resulted in food delivery under a variable-interval 3-min schedule. Responding was suppressed by shock presentation (punishment) but was still positively accelerated throughout each fixed-interval cycle; steady response rates occurred during the alternate component when only the variable-interval schedule was in effect. Overall rates of punished responding were largely unchanged with d-amphetamine (0.1-3.0 mg/kg); unpunished responding was generally either increased slightly or was decreased. Pentobarbital and chlordiazepoxide (1.0-17.0 mg/kg) administered alone increased both punished and unpunished responding at most doses. Combinations of d-amphetamine with either pentobarbital or chlordiazepoxide produced increases in punished responding that exceeded those obtained with either of these drugs alone. The combined effects of d-amphetamine and either pentobarbital or chlordiazepoxide on unpunished responding depended on the individual dose combinations. Combinations of d-amphetamine with pentobarbital or chlordiazepoxide produced effects on both punished and unpunished responding that differed substantially from those obtained when any of these drugs were administered separately.     

Multiple interruptions of responding maintained by a fixed-interval schedule of electric-shock presentation in squirrel monkeys.

Recent experiments have demonstrated that the characteristic pattern of responding engendered by a fixed-interval (FI) schedule of food reinforcement can also be established and maintained by response-contingent electric shocks. Under an FI schedule of food presentation, the characteristic pattern of responding survives repeated interruption by stimulus conditons absent at the time of reinforcement. The present experiment, with 3 male squirrel monkeys, demonstrates a similar phenomenon under circumstances in which the sole consequence of FI responding was the delivery of response-contingent shocks. Several possible interpretations of FI performance maintained by electric-shock presentation are discussed. (15 ref.) (French summary) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tolerance to discriminative stimulus effects of d-amphetamine.

Chronic administration of high doses of d-amphetamine produced time-limited, surmountable tolerance to stimulus effects of d-amphetamine. 23 male Sprague-Dawley rats discriminated saline and 0.80 mg/kg d-amphetamine under fixed ratio (FR) schedules of food delivery. Suspending training and administering saline did not alter sensitivity to d-amphetamine, indicating that neither tolerance nor sensitization developed during regular training. Acute pretreatment with 3.2 mg/kg d-amphetamine did not alter the ED50 for stimulus effects of d-amphetamine. In contrast, administration of 3.2 or 6.4 mg/kg d-amphetamine, b.i.d., for 3 days or 2 weeks increased the ED50 for stimulus effects 3- to 4-fold but did not produce consistent tolerance to rate-altering effects. Tolerance to stimulus effects was surmountable, as higher doses of d-amphetamine produced full drug-lever selection in tolerant rats. Sensitivity recovered after chronic administration ended. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acquisition, maintenance and reinstatement of intravenous cocaine self-administration under a second-order schedule of reinforcement in rats: effects of conditioned cues and continuous access to cocaine

Second order schedules of IV cocaine reinforcement in rats provide a reliable method for evaluating the effects of conditioned stimuli on cocaine-seeking behaviour, and for measuring the motivational aspects of cocaine reinforcement. In the procedure established here, each infusion of cocaine (0.25 mg/infusion) was initially made contingent on a lever press and was paired with a 20-s light conditioned stimulus (CS). When rats acquired stable rates of cocaine self-administration, the response requirement for cocaine was increased progressively to a second-order schedule of the type FI15 min(FR10:S), whereby the IV cocaine infusion was self-administered following the completion of the first FR10 responses (and CS presentation) after a 15-min fixed interval (FI) had elapsed. Evaluation of the animals' responding during the first, drug-free interval of each daily session provided a measure of cocaine-seeking behaviour, independent of other pharmacological effects of the self-administered drug. Thus, a dose-response study (dose range: 0.083, 0.25 and 0.50 mg/infusion) revealed that responding under this schedule during the initial, drug-free interval changed monotonically with dose, whereas an inverse relationship between cocaine dose and response level tended to appear during the rest of the session, after rats had self-administered the drug. Responding under this schedule was also shown to occur under the control of the CS, which had acquired conditioned reinforcing properties. Thus, a decrease in responding and an increase in the latency to initiate responding followed the omission of the CS for 3 consecutive days. In addition, extinction of cocaine-seeking behaviour was slower when contingent CS presentations occurred compared to extinction when the CS was not present. Furthermore, the reinstatement of responding for cocaine, which followed a brief period of non-contingent CS presentations, was retarded when this conditioned reinforcer had been extinguished together with cocaine. Finally, cocaine-seeking behaviour decreased markedly for the first 6 h that followed a 12-h period of continuous access to cocaine, when compared to responding 6 h after a 90-min session of limited access to the drug. Responding subsequently increased to baseline levels within 72 h. These results emphasise the utility of second-order schedules for studying drug-seeking behaviour and the importance of drug-associated cues in maintaining such responding for cocaine.     

Aversive schedules with independent probabilities of reinforcement for responding and not responding by rhesus monkeys: II. Without signal.

Manipulated independently the probabilities of aversive stimulus presentation given the occurrence or the nonocurrence of a leverpress response. 10 naive male rhesus monkeys (Macaca mulatta) were divided into 5 groups, each group receiving a different sequence of the 2 probabilities and thereby a different sequence of electric shock presentation schedules ranging between avoidance and punishment. The schedules provided systematic control both of the amount of response facilitation that occurred when response-produced shocks were first introduced following avoidance training and of the postfacilitation response rate decline. When the probability of shock presentation following a response was less than that for not responding, scalloped response patterns occurred; when the relative shock probabilities were reversed, bipeak response patterns were observed. (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Molecular mechanisms resulting in pathogenic anti-mouse erythrocyte antibodies in New Zealand black mice

A procedure was developed with pigeons to extend the experimental analysis of punished behavior and the effects of anxiolytic drugs. Under this procedure the completion of a fixed-ratio requirement on a changeover key switched between two variable-interval schedules of reinforcement that were programmed on a second response key. Under one schedule, correlated with a green keylight, key pecks produced only food; under the second schedule, correlated with a red keylight, key pecks produced both food and electric shock. Pigeons were switched into the component with shock if they did not enter that component within 5 min. Parameter values of the variable-interval schedules were manipulated systematically and the effects of two clinically active anxiolytic drugs, buspirone and chlordiazepoxide, were examined. Responding was suppressed during the component with shock (punishment) and, under non-drug conditions, pigeons infrequently switched into the punishment component; changeover responses occurred rapidly when switched into the punishment component. Both buspirone (0.1-3.0 mg/kg) and chlordiazepoxide (3.0-30 mg/kg) increased punished responding at doses that had little effect on unpunished responding; d-amphetamine (0.3-5.6 mg/kg), which was studied only under one parameter of the variable-interval schedule, produced greater decreases in rates of punished responding than in unpunished responding.(ABSTRACT TRUNCATED AT 250 WORDS)     

Response suppression to a shock-predicting stimulus in differentially reared monkeys (Macaca mulatta).

Four rhesus monkeys reared in social isolation for the 1st 9 mo of life and 4 monkeys reared with social contact were trained to leverpress for food reinforcement on a VI 60-sec schedule of reinforcement as adults. A 3-min auditory CS that terminated with the delivery of an electric foot shock was then presented at random intervals during each test session. Results indicate that though preshock response rates did not differ, the isolates failed to suppress responding in the presence of the shock-predicting CS at the same rate or to the same degree as did socially reared Ss. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A history of postponing shock does not appear to alter the discriminative stimulus effects of cocaine

Previous research has shown that the rate of punished lever pressing of monkeys is typically decreased by cocaine administration. However, cocaine increases punished responding in monkeys with a history of responding maintained by the postponement of shock presentation. This raises the question of whether other behavioral effects of cocaine differ following a history of postponing shock. The present experiment examined whether a history of postponing shock alters the discriminative stimulus effects of cocaine. Three squirrel monkeys were trained to discriminate cocaine (0.56 mg/kg, intramuscular) from saline. Presses on the left lever produced food following saline injections whereas presses on the right lever were reinforced following administration of cocaine. Occasional test sessions were conducted in which cocaine (0.1-0.56 mg/kg), midazolam (0.03-0.56 mg/kg) or pentobarbital (0.3-5.6 mg/kg) was injected prior to the session and responding on either lever was reinforced. Discrimination training was discontinued during a second experimental phase in which responding was maintained by shock postponement. Pulling a chain postponed mild shocks for 25 s, whereas shocks occurred every 5 s in the absence of responding. Next, the drug discrimination dose-response curves were redetermined. The dose-response curves for all drugs before and after the shock postponement history were similar. This outcome suggests that the influence of a history of shock postponement is specific to punished responding.     

Reinforcement magnitude modulation of rate dependent effects in pigeons and rats.

Response rate can influence the behavioral effects of many drugs. Reinforcement magnitude may also influence drug effects. Further, reinforcement magnitude can influence rate-dependent effects. For example, in an earlier report, we showed that rate-dependent effects of two antidepressants depended on reinforcement magnitude. The ability of reinforcement magnitude to interact with rate-dependency has not been well characterized. It is not known whether our previous results are specific to antidepressants or generalize to other drug classes. Here, we further examine rate-magnitude interactions by studying effects of two stimulants (d-amphetamine [0.32–5.6 mg/kg] and cocaine [0.32–10 mg/kg]) and two sedatives (chlordiazepoxide [1.78–32 mg/kg] and pentobarbital [1.0–17.8 mg/kg]) in pigeons responding under a 3-component multiple fixed-interval (FI) 300-s schedule maintained by 2-, 4-, or 8-s of food access. We also examine the effects of d-amphetamine [0.32–3.2 mg/kg] and pentobarbital [1.8–10 mg/kg] in rats responding under a similar multiple FI300-s schedule maintained by 2- or 10- food pellet (45 mg) delivery. In pigeons, cocaine and, to a lesser extent, chlordiazepoxide exerted rate-dependent effects that were diminished by increasing durations of food access. The relationship was less apparent for pentobarbital, and not present for d-amphetamine. In rats, rate-dependent effects of pentobarbital and d-amphetamine were not modulated by reinforcement magnitude. In conclusion, some drugs appear to exert rate-dependent effect which are diminished when reinforcement magnitude is relatively high. Subsequent analysis of the rate-dependency data suggest the effects of reinforcement magnitude may be due to a diminution of drug-induced increases in low-rate behavior that occurs early in the fixed-interval. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Proactive behavioral effects of theta-driving septal stimulation on conditioned suppression and punishment in the rat.

In 2 experiments, a treatment phase of septal stimulation preceded the acquisition of free operant leverpressing on a random-interval 64-sec reinforcement schedule. 32 male Sprague-Dawley rats were chronically implanted with a bilateral septal stimulating electrode and a unilateral bipolar hippocampal recording electrode. Ss received (a) low-frequency (7.7 Hz) stimulation, which drove the hippocampal theta rhythm; (b) random-pulse stimulation (average frequency 7.7 Hz), which produced only nonregular waveforms in the hippocampus; or (c) no stimulation. After 12 days of leverpress acquisition, Ss were presented while leverpressing with an auditory signal associated with a particular schedule of shock delivery: In Exp I, shocks occurred despite the S's response strategy; in Exp II, shocks were delivered only if the S pressed the lever. In both experiments, leverpressing was suppressed by the auditory stimulus. Theta-driving but not random-pulse septal stimulation proactively increased behavioral tolerance to the effects of electric shock. Results support the idea that proactive behavioral effects of septal stimulation are a consequence of the production of the hippocampal theta rhythm. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clocinnamox antagonism of the antinociceptive effects of mu opioids in squirrel monkeys

The opioid agonists morphine, etorphine, buprenorphine and U50,488 were examined alone and in combination with the insurmountable opioid antagonist clocinnamox (C-CAM) in squirrel monkeys responding under a schedule of shock titration. In this procedure, shock intensity increased every 15 sec from 0.01 to 2.0 mA in 30 increments. Five lever presses during any given 15-sec shock period produced a 15-sec timeout, after which shock resumed at the next lower intensity. When given alone, each of these agonists increased the median intensity at which the monkeys maintained shock [median shock level (MSL)]. At the highest dose examined alone, each agonist produced maximal increases in MSL and, except buprenorphine, decreased response rates. C-CAM dose-dependently antagonized the effects of morphine, etorphine and buprenorphine on MSL. In the presence of the higher C-CAM doses, etorphine, morphine and buprenorphine did not produce maximal effects on MSL. The effects of U50,488 were not systematically altered when tested in combination with the highest C-CAM dose. In general, C-CAM was more potent and the duration of antagonism was slightly longer against buprenorphine than against morphine and etorphine. Quantitative analysis of these data according to an extended model of yielded the following apparent affinity and efficacy estimates, respectively: etorphine (0. 085 mg/kg, 117); morphine (49 mg/kg, 24) and buprenorphine (0.62 mg/kg, 7.1). Determination of the individual q values over time indicated that the receptor population recovers more quickly after C-CAM antagonism of etorphine than from C-CAM antagonism of either morphine or buprenorphine. These data suggest that C-CAM functions as a long-lasting antagonist of mu opioid agonist actions in a shock titration procedure and yields estimates of relative intrinsic efficacy with the rank order of etorphine > morphine > buprenorphine.     

Covariation bias in panic-prone individuals.

Covariation estimates between fear-relevant (FR; emergency situations) or fear-irrelevant (FI; mushrooms and nudes) stimuli and an aversive outcome (electrical shock) were examined in 10 high-fear (panic-prone) and 10 low-fear respondents. When the relation between slide category and outcome was random (illusory correlation), only high-fear participants markedly overestimated the contingency between FR slides and shocks. However, when there was a high contingency of shocks following FR stimuli (83%) and a low contingency of shocks following FI stimuli (17%), the group difference vanished. Reversal of contingencies back to random induced a covariation bias for FR slides in high and low-fear respondents. Results indicate that panic-prone respondents show a covariation bias for FR stimuli and that the experience of a high contingency between FR slides and aversive outcomes may foster such a covariation bias even in low-fear respondents. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of d-amphetamine, pentobarbital, chlorpromazine and promazine on electric shock postponement responding by the pigeon

The effects of d-amphetamine, pentobarbital, chlorpromazine and promazine on responding under schedules of electric shock postponement were studied in pigeons. Responding was maintained by three different response-shock intervals (10, 20 and 60 seconds). Low doses (0.3-3 mg/kg) of d-amphetamine increased response rates without decreasing shock rates under all three response-shock intervals. The highest dose (10 mg/kg) of d-amphetamine increased the shock rates under all response-shock intervals and decreased the high response rate under the 10-second response-shock interval but did not decrease the lower rates of responding under the 20- and 60-second response-shock intervals. Pentobarbital decreased the high rate of responding maintained under the 10-second response-shock interval at lower dose (10 mg/kg) than the lower rates of under the 20- and 60-second response-shock intervals. The high dose (17.5 mg/kg) of pentobarbital decreased responding and the low doses (1-3 mg/kg) had no effect under all three response-shock intervals. Chlorpromazine (3-100 mg/kg) did not affect the average rate of responding under all response-shock intervals and only slightly increased shock rates under the 20- and 60-second response-shock intervals. Promazine (3-30 mg/kg) increased the rates of responding and decreased shock rates under all three response-shock intervals. Analysis of the temporal patterns of responding within the response-shock interval showed that d-amphetamine tended to induce the animals to respond earlier than they normally would in the response-shock interval while otherwise maintaining the temporal pattern of responding, pentobarbital decreased the probability of responses late in the response-shock interval, and chlorpromazine and promazine increased the probability of responses in the middle of the response-shock interval, producing a lessening of the temporal patterning of responding within the response-shock interval.     

Covariation bias in flight phobics

Covariation estimates (CEs) between fear-relevant (FR) stimuli (slides of airplane crash sites) or fear-irrelevant (FI) stimuli (slides of airplanes in flight or mushrooms) and an aversive outcome (electrical shock) were examined in 15 flight phobics (high-fear participants) and 15 non-flight-phobic individuals (low-fear participants) by means of an illusory correlation experiment. In spite of a random relationship between all slide categories and outcome (illusory correlation), flight phobics exhibited a covariation bias and showed higher CEs for the contingency between FR slides and shocks than for the contingency between FI slides and shocks in a first experimental block. The CEs of flight phobics for FR slides and shocks was significantly higher than that of non-flight-phobic individuals, while high- and low-fear participants did not differ in their CEs for the other slide-shock combinations. However, even high-fear individuals were able to correct their initial covariation bias in subsequent illusory correlation blocks, presumably based on disconfirming situational information.     

Simultaneous and backward fear conditioning in the rat.

Examined simultaneous and backward Pavlovian conditioning paradigms using a UCS event which was longer in duration than the CS. 3 experiments with male Sprague-Dawley rats (N = 96) paired a 4-sec electric shock with a 2-sec tone-light stimulus under conditions in which the onset of the stimulus occurred 0, .25, 1.0, 2.0, 4.0, or 4.5 sec. after the onset of the shock. Relative to nonpaired control procedures, response-contingent presentations of the CSs in these paradigms significantly suppressed a food-rewarded free operant, indicating that these temporal relationships can produce excitatory associative conditioning. It is suggested that the distinctions between "forward," "simultaneous," and "backward" procedures be modified to include a more molecular analysis of the UCS event. (21 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pavlovian and instrumental determinants of response suppression in the pigeon.

Exp I demonstrated the formation of a discriminated punishment effect in the absence of a conditioned emotional response. Electric shocks were delivered at random intervals to 3 naive male White Carneaux pigeons pecking for food on a variable-interval schedule. During a 1-min visual conditioned stimulus (CS), scheduled shocks were delayed until a response occurred (punishment). Differential suppression to the CS was observed in addition to overall suppression. Suppression was related to shock intensity. In Exp II with the same Ss, CS suppression was related to the CS and was not an artifact of response pattern or discrimination of shock patterns. The punishment contingency without the CS did not suppress behavior, and the CS without the punishment contingency did not relieve suppression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of postnatal exposure to a PCB mixture in monkeys on multiple fixed interval-fixed ratio performance

Behavioral impairment as a consequence of PCB exposure beginning in utero has been reported in both humans and animals. The present study assessed the behavioral consequences of postnatal exposure to PCBs. Male monkeys (Macaca fascicularis) were dosed from birth to 20 weeks of age with 7.5 microgram(s)/kg/day of a PCB mixture representative of the PCBs typically found in human breast milk (eight monkeys) or vehicle (four monkeys). At 4 years of age, performance under a multiple fixed interval (FI)-fixed ratio (FR) schedule of reinforcement was assessed. The FI component was more sensitive to disruption as a result of PCB exposure than was the FR component. PCB-exposed monkeys displayed shorter mean interresponse times (IRTs) than controls, particularly during the earlier sessions of the experiment. Similarly, the increase in pause time characteristic of the acquisition of typical FI performance emerged more slowly across sessions in the PCB-treated group. However, the number of short IRTs (less than 5 s) remained greater in the treated group compared to controls over the 48-session duration of the experiment. On the FR component, control monkeys decreases the mean pause time across sessions whereas the PCB-treated group did not; there were no differences between groups for absolute value of average IRT or pause time. The results of this study extend previous research in this cohort of monkeys, and provide further evidence that PCB exposure limited to the early postnatal period and resulting in environmentally relevant body burdens produces long-term behavioral effects.     

Feeding conditions alter the demand for phencyclidine and ethanol: A behavioral analysis.

This experiment examined the effects of feeding conditions on orally self-administered phencyclidine (PCP) or ethanol in rhesus monkeys using a behavioral≡oral economic analysis. Drug intake was measured as a function of drug cost, which was varied by changes in the fixed ratio (FR) schedule. The monkeys were trained to respond for PCP (0.25 mg/ml) or ethanol (8% wt/vol) with concurrent water available under FR 4-128 schedules. As the FR increased. drug intake decreased in a positively decelerating manner. Results suggest that food deprivation increased the reinforcement value of the drugs as well as significantly increasing consumption of both PCP and ethanol. In addition, ethanol and PCP deliveries showed proportionally greater increases due to food deprivation as FR increased. Together, these results suggest that food deprivation increases the reinforcing efficacy of drugs and this eifect is enhanced as the cost (FR) of the drug increases. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Selective associations in one-day-old rats: Taste–toxicosis and texture–shock aversion learning.

Three experiments investigated cue-consequence specificity and long-delay learning in 187 1-day-old Sprague-Dawley rats and determined whether selective associations are accompanied by long-delay learning early in life. Ss learned aversions to a novel taste paired with Li-induced distress and to a tactile stimulus paired with brief electric shocks. However, aversions did not develop when taste was paired with shock or when the tactile stimulus was paired with Li treatment. The aversions occurred only when Li treatment immediately followed taste exposure and when shock was concurrent with exposure to the tactile stimulus. Findings indicate that selective associations in aversion learning are mediated by innate mechanisms that govern conditioning in the absence of extensive ontogenetic experience and show that selective associations are not sufficient for the occurrence of long-delay learning. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)