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W C Hardwick

Publications and source records attributed to W C Hardwick.

At least 19 recordsLinked to original sources
PubMed2002

Drug discrimination under concurrent variable-ratio variable-ratio schedules.

Pigeons were trained to discriminate 5 mg/kg pentobarbital from saline under concurrent variable-ratio (VR) VR schedules, in which responses on the pentobarbital-biased lever were reinforced under the VR schedule with the smaller response requirements when pentobarbital was given before the session, and responses on the saline-biased key were reinforced under the VR schedule with the larger response requirements. When saline was administered before the session, the reinforcement contingencies associated with the two response keys were reversed. When responding stabilized under concurrent VR 20 VR 30, concurrent VR 10 VR 40, or concurrent VR 5 VR 50 schedules, pigeons responded almost exclusively on the key on which fewer responses were required to produce the reinforcer. When other doses of pentobarbital and other drugs were substituted for the training dose, low doses of all drugs produced responding on the saline-biased key. Higher doses of pentobarbital and chlordiazepoxide produced responding only on the pentobarbital-biased key, whereas higher doses of ethanol and phencyclidine produced responding only on this key less often. d-Amphetamine produced responding primarily on the saline-biased key. When drugs generalized to pentobarbital, the shape of the generalization curve under concurrent VR VR schedules was more often graded than quantal in shape. Thus, drug discrimination can be established under concurrent VR VR schedules, but the shapes of drug-discrimination dose-response curves under concurrent VR VR schedules more closely resemble those seen under interval schedules than those seen under fixed-ratio schedules. Graded dose-response curves under concurrent VR VR schedules may relate to probability matching and difficulty in discriminating differences in reinforcement frequency.

Animals↗
PubMed2001

Schedule control of quantal and graded dose-effect curves in a drug-drug-saline discrimination.

Pigeons were trained to discriminate among 5 mg/kg pentobarbital, 5 mg/kg morphine, and saline when responding was maintained under fixed-interval (FI) or fixed-ratio (FR) reinforcement schedules. After the discrimination was established, other drugs were substituted for the training drugs. After low doses of pentobarbital and chlordiazepoxide, responding shifted from the saline key to the pentobarbital key under both FR and FI schedules. After low doses of morphine and methadone, responding shifted from the saline key to the morphine key under both reinforcement schedules. After all doses of d-amphetamine, responding occurred largely on the saline key under both schedules. Responding also was confined largely to the saline key after phencyclidine administration under the FR schedule, but under the FI schedule, responding shifted from the saline key to the pentobarbital key at high doses of phencyclidine. When responding was maintained under the FR schedule, the dose-response curves for drugs that generalized to the training drugs were quantal in shape, while under the FI schedule, the dose-response curves for drugs that generalized to the training drugs were graded. These data extend observations that FR schedules generate quantal dose-response curves, and FI schedules generate graded dose-response curves to complex three-key drug discriminations.

Animals↗
PubMed2001

Discrimination of pentobarbital doses and drug mixtures under fixed-ratio and fixed-interval reinforcement schedules.

Pigeons were trained to discriminate among 5 mg/kg pentobarbital, 10mg/kg pentobarbital, and saline, under either fixed-interval (FI) or fixed-ratio (FR) reinforcement schedules. When baseline responding stabilized, a higher percentage of responses occurred on the key that produced the reinforcer under the FR schedule than under the FI schedule. After low doses of pentobarbital, responding shifted from the saline key to the 5 mg/kg pentobarbital key; at higher doses of pentobarbital responding shifted to the 10mg/kg pentobarbital key under both schedules. After low doses of ethanol and chlordiazepoxide, responding shifted from the saline key to the 5 mg/kg pentobarbital key, but after high doses of these drugs, responding continued to occur on the 5 mg/kg pentobarbital key under both reinforcement schedules. A 5 mg/kg dose of pentobarbital increased responding on the 10 mg/kg pentobarbital key when it was combined with pentobarbital, ethanol or chlordiazepoxide. Phencyclidine and D-amphetamine produced responding largely on the saline key under both reinforcement schedules. Under the FR schedule, pentobarbital dose-response curves were usually quantal, whereas under the FI schedule the pentobarbital dose-response curves usually were graded.

Animals↗
PubMed2000

Drug discrimination in rats under concurrent variable-interval variable-interval schedules.

Eight rats were trained to discriminate pentobarbital from saline under a concurrent variable-interval (VI) VI schedule, on which responses on the pentobarbital-biased lever after pentobarbital were reinforced under VI 20 s and responses on the saline-biased lever were reinforced under VI 80 s. After saline, the reinforcement contingencies programmed on the two levers were reversed. The rats made 62.3% of their responses on the pentobarbital-biased lever after pentobarbital and 72.2% on the saline-biased lever after saline, both of which are lower than predicted by the matching law. When the schedule was changed to concurrent VI 50 s VI 50 s for test sessions with saline and the training dose of pentobarbital, responding on the pentobarbital-biased lever after the training dose of pentobarbital and on the saline-biased lever after saline became nearly equal, even during the first 2 min of the session, suggesting that the presence or absence of the training drug was exerting minimal control over responding and making the determination of dose-effect relations of drugs difficult to interpret. When the pentobarbital dose-response curve was determined under the concurrent VI 50-s VI 50-s schedule, responding was fairly evenly distributed on both levers for most rats. Therefore, 6 additional rats were trained to respond under a concurrent VI 60-s VI 240-s schedule. Under this schedule, the rats made 62.6% of their responses on the pentobarbital-biased lever after pentobarbital and 73.5% of their responses on the saline-biased lever after saline, which also is lower than the percentages predicted by perfect matching. When the schedule was changed to a concurrent VI 150-s VI 150-s schedule for 5-min test sessions with additional drugs, the presence or absence of pentobarbital continued to control responding in most rats, and it was possible to generate graded dose-response curves for pentobarbital and other drugs using the data from these 5-min sessions. The dose-response curves generated under these conditions were similar to the dose-response curves generated using other reinforcement schedules and other species.

Animals↗
PubMed2000

Effect of drugs on response-duration differentiation VII: response-force requirements.

Rats were trained to press a lever for at least 1 s but for less than 1.3 s. The force required to press the lever was then increased or decreased by 10, 15, or 20 g. Increases in the force requirements for lever pressing decreased timing accuracy, but decreases in the force requirement had the opposite effect. Accuracy decreases at increasing force requirements were characterized by an increase in the relative frequency of responses that were too short to meet the reinforcement criterion. In contrast, increases in accuracy when the force requirements were decreased were characterized by increases in response durations that met the reinforcement criterion and decreases in the relative frequency of responses that were too short to produce the reinforcer. Phencyclidine (PCP) and methamphetamine produced dose-dependent decreases in accuracy that were associated primarily with increases in the relative frequency of short response durations, although methamphetamine also produced increases in long response durations at some doses. When the effects of PCP were determined with the force requirement increased by 10 g or decreased by 15 g, the cumulative response-duration distribution shifted toward even shorter response durations. When the effects of methamphetamine were determined with the force requirement on the lever increased by 10 g, the cumulative frequency distribution was shifted toward shorter response durations to about the same extent as it had been before force requirements increased; however, when the force required to press the lever was decreased by 15 g, these shifts toward shorter response durations almost completely disappeared. These results show that increases and decreases in the force requirements for lever pressing have different effects on the accuracy of temporal response differentiation.

Animals↗
PubMed1997

Discriminative stimulus effects and antipunishment effects of drugs measured during the same session.

The effects of pentobarbital, diazepam, phencyclidine, buspirone and methamphetamine on drug discrimination and on responding under a variable-interval variable-interval with punishment schedule were studied in pigeons trained to discriminate 5.0 mg/kg pentobarbital from saline. Pentobarbital produced dose-dependent increases in the proportion of responses on the drug key and on rates of punished responding. Diazepam had very similar effects except that the dose-effect curve for punished responding turned over at the highest dose level. Phencyclidine produced only partial responding on the drug key and weakly increased punished responding. Buspirone produced small increases in punished responding, but in the drug discrimination experiments buspirone did not cause responding on the drug key. Methamphetamine did not produce responding on the drug key, nor did it increase rates of punished responding. These experiments are among the first to demonstrate that drug discrimination and other behaviors can be studied within single test sessions in the same animals and they suggest that there is a close correspondence between the discriminative stimulus effects of some drugs and their anti-punishment activity.

Animals↗
PubMed1997

Drug discrimination under a concurrent fixed-interval fixed-interval schedule.

Pigeons were trained to discriminate 5.0 mg/kg pentobarbital from saline under a concurrent fixed-interval (FI) FI schedule of food presentation on which, after pentobarbital administration, responses on one key were reinforced with food under an FI 60-s component and responses on the other key were reinforced under an FI 240-s component. After saline administration, the schedule contingencies on the two keys were reversed. After both pentobarbital and saline, pigeons responded more frequently on the key on which responses had been programmed to produce the reinforcer under the FI 60 component of the concurrent schedule. The schedule was changed to concurrent FI 150 FI 150 s for drug-substitution tests. In each bird, increasing doses of pentobarbital, ethanol, and chlordiazepoxide produced increases in the proportion of responses on the key on which responses had been reinforced under the FI 60 component after pentobarbital administration during training sessions. The proportion of responses on that key was slightly lower for ethanol than for chlordiazepoxide and pentobarbital. At a dose of pentobarbital higher than the training dose, responding decreased on the key that had been reinforced under the FI 60 component during training sessions. Phencyclidine produced less responding on the key programmed under the FI 60-s component than did pentobarbital. Methamphetamine produced responding primarily on the key on which responses had been reinforced under the FI 60-s component after saline administration.

Animals↗
PubMed1996

Effects of drug discrimination history on the generalization of pentobarbital to other drugs.

In pigeons trained to discriminate between pentobarbital and saline, pentobarbital, amobarbital and diazepam substituted for pentobarbital, whereas phencyclidine (PCP) substituted in part for pentobarbital and d-amphetamine, morphine and drug vehicles did not substitute. After morphine replaced pentobarbital as the training drug (group A), morphine, pentobarbital and diazepam substituted, PCP substituted in part, but not d-amphetamine, haloperidol and vehicles. After d-amphetamine replaced pentobarbital as the training drug (group B), d-amphetamine, pentobarbital and diazepam substituted, PCP substituted in part, but not haloperidol, morphine and vehicles. Next, morphine and d-amphetamine were reversed as training drugs for the two groups. In group A, morphine, d-amphetamine, pentobarbital and diazepam substituted, PCP substituted in part, but not haloperidol and vehicles. Similar effects were observed in group B. Next, birds in group A were reinforced for responses on the drug key (red key) after d-amphetamine and on the previous saline key (green key) after pentobarbital. In group B, morphine continued as the training drug for the red key, whereas responses on the green key were reinforced after pentobarbital. In group A, d-amphetamine, morphine, d-pentazocine and to some extent PCP, produced responding on the red key, whereas pentobarbital, diazepam, haloperidol and the vehicles produced responding on the green key. Similar results were obtained in group B. Finally, responses were reinforced on the green key after pentobarbital and on the red key after saline. Group B did not learn this discrimination. In group A, responding occurred on the red key after d-amphetamine, morphine, haloperidol and vehicles, in part after d-pentazocine, but not after pentobarbital, diazepam and PCP. These experiments show that drug stimuli can continue to exert stimulus control over behavior for long periods, even when training with several other drug stimuli intervenes between tests, and the experiments also show that through sequential training procedures multiple drugs can serve as discriminative stimuli for the same response, even when these drugs are from different phamacological classes.

Animals↗
PubMed1995

Effects of access to a running wheel on food, water and ethanol intake in rats bred to accept ethanol.

Rats from the University of Indiana lines bred to accept ethanol (P rats) and not to accept ethanol (NP rats) were divided into two groups of 3 rats per group. The first group of P and NP rats was given free access to food, water and 5% (w/v) ethanol 24 h a day. After food, water and ethanol intake stabilized, a running wheel was introduced into the cage. Access to the running wheel decreased ethanol intake and increased water intake in P rats. When the running wheel was locked in place, ethanol intake by P rats increased, but when the wheel was unlocked again, no decrease in ethanol intake occurred. Access to the running wheel did not affect food, water or ethanol intake in NP rats. The decrease in ethanol intake when the running wheel was introduced was replicated in the second group of P rats exposed to 5% ethanol and later to 10% ethanol. The decreases in ethanol consumption produced by the introduction of a running wheel for this genetic model of alcohol consumption are similar to those previously reported using schedule-induced polydipsia to induce ethanol intake.

Alcohol Drinking↗
PubMed1994

Effects of drugs on response duration differentiation. III. Acute variation of reinforced duration.

Rats trained to hold a lever down for at least 1.0 s but less than 1.3 s could differentiate the reinforced response duration on about 50% of the trials. The response duration frequency distribution was a normal distribution with a peak near the minimum reinforced response duration. Dose-effect curves were determined for the effects of phencyclidine (PCP) and methamphetamine. Subsequently, rats continued to be trained for 3 days a week with responses between 1.0 and 1.3 s reinforced, but on days when injections were given either the maximum reinforced duration was increased to 2.3 s, or the minimum reinforced duration was lowered to 0.5. When the maximum duration was increased to 2.3 s, the percentage of reinforced responses increased to 60% and when the minimum reinforced duration was decreased to 0.5 s, the percentage of reinforced responses increased to 89%. Despite the increased percentage of reinforced responses when the time window was widened, the effects of PCP and methamphetamine were not changed. These data suggest that the effects of drugs on response duration differentiation are not greatly influenced by transient changes in reinforcement frequency.

Animals↗
PubMed1991

Effects of drugs that bind to PCP and sigma receptors on punished responding.

Several arylcyclohexylamines and opioid benzomorphans that bind to phencyclidine (PCP) receptors were studied for their effects on punished and unpunished responding maintained under fixed-interval schedules of food presentation. All of these drugs increased both punished and unpunished responding, although higher doses decreased responding. The order of potency for increasing punished responding was MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzoa(a,d)-cyclohepten-5,1 0-imine] greater than [1-[1-(2-thienyl)cyclohexyl]piperidine] = PCP greater than (+)-N-allylnormetazocine = (-)-N-allynormetazocine. There was a high correlation (0.95) between the relative potency of these drugs in increasing punished responding and their relative affinity for PCP receptors. Because some of these drugs also bind to sigma receptors, drugs with a high affinity for sigma receptors, such as haloperidol, BD 737 [1S,2R-(-)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-N- methyl-2-(1-pyrrolidinyl) cyclohexylamine] and (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine, were also studied for their effects on punished and unpunished responding. These drugs produced only rate-decreasing effects. The correlation between the relative potency of drugs in increasing punished responding and their relative affinity for sigma receptors was low (-0.19). These data suggest that the PCP receptor is involved in some drug-induced increases in punished responding.

Animals↗
PubMed1990

Phencyclidine pharmacokinetics and concentration-response relationships in the pigeon.

Phencyclidine (PCP) pharmacokinetics and drug discrimination were examined in pigeons (n = 6 in both groups) after intramuscular doses of 1.48 mg/kg. PCP absorption was rapid with maximum measured plasma concentrations ranging from 559 to 1450 ng/ml at 10-30 min after dosing, which corresponded to the time of maximum PCP stimulus effects in the drug discrimination studies. The terminal elimination half-life was 0.88 hr (harmonic mean). Average values for the volume of distribution and total body clearance were 1.6 l/kg and 18.2 ml/min/kg, respectively. In the behavioral studies, pigeons discriminated PCP-like effects from about 2 min to 2 hr after dosing. An average value for response on the PCP-appropriate key and for PCP concentration at each time point from 2 min to 2 hr was calculated from the individual subject data. Least-squares linear regression analysis of these data showed a highly significant relationship between the ability to discriminate PCP and log PCP concentration (y = 103x - 219, r2 = .810, p less than 0.005). This analysis suggests PCP concentration is a good predictor of behavioral efficacy.

Animals↗
PubMed1987

Phencyclidine pharmacokinetic scaling among species.

Interspecies pharmacokinetic parameters (y) for phencyclidine [1-(1-phenylcyclohexyl)piperidine] were correlated with body weight (B) using linear regression and the allometric equation of the form y = aBx (which also may be written as the linear regression equation, log y = x log B + log a). The data were obtained from previously reported pharmacokinetic studies in mammals (i.e., humans, monkey, dog, rat and mouse) and new pharmacokinetic data for the pigeon. The animal body weights ranged from 32.5 to 77,000 g and included 6 animal species from 2 vertebrate classes. The pharmacokinetic parameters correlated with body weight were T1/2 (T1/2 = 126B0.32, r2 = 0.799), volume of distribution (V beta = 10B0.96, r2 = 0.966) and systemic clearance (CLs = 50B0.64, r2 = 0.891). In addition, clearance values were multiplied by the maximum lifespan potential (MLP) of each animal and correlated with body weight [CLs X MLP = (3.3 X 10(5))B1.0, r2 = 0.991]. This helped normalize for species differences in systemic clearance, which correlated with species longevity. These allometric equations should provide the information for scaling phencyclidine pharmacokinetic data among diverse species.

Animals↗
PubMed1986

Relationship of plasma phencyclidine levels to phencyclidine discrimination in the pigeon.

Plasma phencyclidine levels were determined in pigeons trained to discriminate 1.5 mg/kg phencyclidine from saline under a second-order schedule using a color-tracking procedure. With both cumulative and non-cumulative dosing procedures, pigeons reliably discriminated plasma phencyclidine levels above 200 ng/ml. When the time course of phencyclidine discrimination was determined and compared with the time course of phencyclidine levels in plasma in a different group of birds, a similar relationship between discrimination and plasma phencyclidine was generally observed. Plasma phencyclidine levels did not correlate well with position responding observed in some birds after lower phencyclidine doses.

Animals↗
PubMed1985

The effects of triethyltin and trimethyltin in rats responding under a DRL schedule of reinforcement.

Rats were trained to respond under a schedule of reinforcement in which only those responses separated by a 10-to 14-sec period of no responding produced a feed pellet (DRL 10 to 14 sec). Each rat received a single dose of trimethyltin (TMT) (5.6, 7.5, or 10 mg/kg) or triethyltin (TET) 1, 3, 4.25, or 5.6 mg/kg). The lowest dose of TMT (5.6 mg/kg) and the lowest dose of TET (1 mg/kg) were without significant effect. At 7.5 mg/kg and 10 mg/kg TMT, the percentage of the total responses spaced 10 to 14 sec apart decreased over the first 8 to 12 days after TMT. Those rats receiving 7.5 mg/kg TMT gradually returned to control values over the next 2 to 3 weeks while those rats receiving 10 mg/kg never recovered. Rats receiving 3, 4.25, and 5.6 mg/kg TET showed a decrease in the percentage of reinforced responses immediately after receiving TET. The behavior of those rats receiving 3 mg/kg returned to control values in 24 hr. Following 4.25 mg/kg TET, the health of the rats deteriorated rapidly. They were kept alive through heroic measures, but then were killed after testing on the 12th day following TET due to their failing health. At 5.6 mg/kg, the rats were killed on the 4th day due to failing health. These results indicate that TMT and TET differ with respect to potency and time course. The behavioral deficits produced by TET parallel the time course of general toxicity while the behavioral effects of acute TMT administration can persist in time long after the general appearance of the rats has returned to normal.

Animals↗
PubMed1984

Digital intubation.

Digital tracheal intubation provides a safe and efficient method of intubation when the conventional methods of endotracheal intubation are impractical or impossible. Because of difficulties encountered in the field with oral or nasal intubation, a more efficient method was sought. After paramedics were taught tactile intubation on mongrel dogs and human cadavers, the procedure was used on 66 patients in the field over a period of 20 months. Fifty-eight patients were intubated successfully using this method. In 27 of these patients, delay in airway control would have resulted if not for the institution of digital intubation. In seven cases digital intubation was unsuccessful and the patients had to be intubated by other methods. Digital tracheal intubation is a safe, rapid method of intubation and should be considered when other methods prove difficult or impossible.

Emergencies↗
PubMed1983

Effects of barbiturates in rats tolerant to delta 9-tetrahydrocannabinol.

Rats, whose behavior was maintained under a multiple fixed-ratio fixed-interval schedule of food presentation, were given delta 9-tetrahydrocannabinol (delta 9-THC), pentobarbital, barbital, and d-amphetamine before, during and after chronic delta 9-THC administration. Low doses of the barbiturates and d-amphetamine increased rates of responding, especially under the fixed-interval component. Higher doses of all four drugs decreased rates of responding under both schedule components. Tolerance developed to the rate-decreasing effects of delta 9-THC and there was cross tolerance to the rate-decreasing effects of pentobarbital and to a lesser extent barbital, but not to the rate-decreasing effects of d-amphetamine. During chronic delta 9-THC administration, rate-increasing effects of pentobarbital and barbital continued to occur, but the rate-increasing effects of d-amphetamine were attenuated. A second group of rats whose behavior was maintained under a variable-interval schedule of food presentation were given delta 9-THC and barbital before and during chronic barbital administration. Low doses of barbital increased rates of responding and higher doses of both drugs decreased rates. Tolerance developed to the rate-decreasing effects of barbital and there was cross tolerance to delta 9-THC. No tolerance developed to the rate-increasing effects of barbital. Thus, there is cross tolerance between barbiturates and delta 9-THC for rate-decreasing effects on schedule-controlled behavior, but neither tolerance nor cross tolerance occurs for rate-increasing effects.

Animals↗