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Biomedical subjects

W C Hardwick

Publications and source records attributed to W C Hardwick.

9 recordsLinked to original sources
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↗
PubMed1980

Effects of drugs on behavior in rats maintained on morphine, methadone or pentobarbital.

Dose-effect curves were determined for the effects of drugs on responding under a multiple fixed-ratio 10-response fixed-interval 90-sec schedule of food presentation before and during chronic exposure to drugs in the drinking water. In rats consuming 70 to 90 mg/kg of morphine per day, the dose-effect curves for the rate-decreasing effects of morphine on responding under both schedule components shifted 1/2 log unit to the right, but the dose-effect curves for methadone, pentobarbital and d-amphetamine showed little change. In rats consuming 30 to 55 mg/kg of methadone per day there was little change in the dose-effect curves for the rate-decreasing effects of methadone and d-amphetamine on responding, but the dose-effect curve for morphine shifted 1/2 log unit to the right and the dose-effect curve for pentobarbital shifted upward and to the right. In rats consuming 40 to 50 mg/kg of pentobarbital per day, the dose-effect curve for the rate-decreasing effects of pentobarbital shifted to the right by about 1/4 log unit, and there was a similar but less marked shift to the methadone dose-effect curve to the right. In rats consuming pentobarbital, the morphine dose-effect curve was little changed. These experiments suggest that chronic methadone consumption confers greater tolerance to the effects of morphine on schedule-controlled behavior than it confers upon itself, while chronic morphine consumption confers greater tolerance to its own behavioral effects than it does to those of methadone. There appears to be some reciprocal cross-tolerance between methadone and pentobarbital for schedule-controlled behavior, but not between morphine and pentobarbital.

Animals↗