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Biomedical subjects

W L Woolverton

Publications and source records attributed to W L Woolverton.

At least 127 records · Page 7Linked to original sources
PubMed1983

The effect of d-amphetamine and haloperidol alone and in combination on milk drinking in rats.

The effects of d-amphetamine (0.5-4.0 mg/kg IP) and haloperidol (0.015-1.0 mg/kg IP) alone and in combination on intake of a sweetened milk solution were determined in rats. Experimental sessions consisted of a 15-min access to the milk solution once a day, 7 days a week. d-Amphetamine was administered 15 min prior to the session and haloperidol was administered 60 min prior to the session. The interaction of these compounds was determined by repeated determination of the dose-response function for d-amphetamine in combination with different doses of haloperidol. When given alone, each drug produced a dose-dependent decrease in milk intake. In combination with haloperidol, the decrement caused by d-amphetamine was shifted to lower doses in a dose-dependent manner. Isobolographic analysis of the interaction indicates that the intermediate doses (0.03-0.06 mg/kg) of haloperidol were additive and the highest doses (0.12-0.25 mg/kg) of haloperidol were infraadditive with d-amphetamine. Dose-dependent neuropharmacological actions of these compounds may account for dose-dependent interactions.

Animals↗
PubMed1983

Effects of local anesthetics on fixed-interval responding in rhesus monkeys.

Several local anesthetics of both the ester and amide type were administered IM to rhesus monkeys trained to respond on a fixed-interval 5 min schedule of food delivery. With the exception of procainamide, all local anesthetics produced dose-related decreases in response rates. Effects on pattern of responding varied between local anesthetics. With some (cocaine, dimethocaine and lidocaine), rate-dependent effects were apparent. When control rates were low, these compounds increased rates; when control rates were high, they decreased rates. However, with others (procaine, chloroprocaine, tetracaine and propoxycaine) no rate-dependent effects were noted; i.e., these compounds had little or no effect on the pattern of responding, even at doses that substantially reduced response rates. Consistent with other experiments with these compounds, cocaine was the most potent of the group. In several instances, local anesthetics which had similar stimulus properties in other behavioral paradigms differed in terms of their effects on fixed-interval behavior.

Anesthetics, Local↗
PubMed1983

Intragastric self-administration in rhesus monkeys under limited access conditions: methodological studies.

Rhesus monkeys were trained to self-administer psychoactive drugs by the intragastric route of administration under limited access conditions and intermittent schedules of drug delivery. Under a fixed-ratio 10 schedule, pentobarbital, diazepam, and cocaine maintained self-administration in some monkeys. Responding was not maintained by d-amphetamine under these conditions. Under fixed-ratio 10 (timeout 2 min) conditions, cocaine maintained self-administration in all animals (5/5) tested, while pentobarbital maintained responding in 2/3. At doses higher than that which maintained maximal rates, responding was inversely related to dose/injection. Drug intake was relatively constant across dose/injection of cocaine, but was a direct function of dose/injection of pentobarbital and diazepam. The procedure may be useful in assessing behavioral and pharmacological variables controlling oral self-administration of drugs.

Animals↗
PubMed1983

Effects of psychomotor stimulants, alone and in pairs, on milk drinking in the rat after intraperitoneal and intragastric administration.

The effects of cocaine, d-amphetamine and l-cathinone, alone and in pairs, on intake of a sweetened milk solution were determined in rats. Experimental sessions consisted of 15 min access to the milk solution daily, 7 days a week. After the determination of base-line intake, rats were assigned to one of two groups. All rats in one group received i.p. injections 15 min before the session and all rats in the other group received intragastric (i.g.) infusions 30 min before the session. A series of dose-response functions were then determined by giving a dose of a drug or a pair of drug doses once every 4 days. A wide range of doses of both drugs were tested in combination to fully characterize any interactions. When given alone, all three drugs produced dose-dependent decreases in milk intake. For each drug, higher doses were required to decrease milk intake when given i.g. than when given i.p. The decreasing order of potencies was d-amphetamine, l-cathinone and cocaine after i.p. administration and l-cathinone, d-amphetamine and cocaine after i.g. administration. In nearly every case, for both routes of administration, a drug produced dose-dependent shifts to the left of the dose-response function of the drug with which it was combined. Isobolographic analysis of the interactions indicates that d-amphetamine and l-cathinone were infra-additive (i.p.) or additive (i.g.), cocaine and d-amphetamine tended toward supra-additivity by both routes and l-cathinone and cocaine were additive or infra-additive by the i.p. route. The results of the i.g. cocaine and l-cathinone interactions could not be analyzed with isobolograms. The type of interaction was dependent on the particular drug pair, the particular dose combination tested and the route of administration.

Alkaloids↗
PubMed1982

Reinforcing properties of clonidine in rhesus monkeys.

Intravenous clonidine self-administration was studied in rhesus monkeys under conditions of limited and unlimited access. Limited access consisted of daily 2-h experimental sessions with drug available on a fixed ratio 10 schedule. For unlimited access, drug was available 23 h/day with each response resulting in an injection. In all animals under both conditions, responding was maintained at levels that were above those maintained by saline injections at doses between 0.3 and 10 microgram/kg/inj, and the number of injections taken per session depended upon the dose. Under conditions of limited access, peak self-administration rates varied between animals but averaged approximately 30 inj/session. Total session intake was occasionally in excess of 1.0 mg/kg. Under conditions of unlimited access animals frequently self-administered more than 300 inj/day and intakes averaging 3.6 mg/kg/day occurred at the highest dose tested (10 microgram/kg/inj). When saline was substituted for clonidine after periods of clonidine access that ranged from 10-40 days, withdrawal signs included facial flushing, refusal of preferred food, restlessness, salivation, and emesis. These signs could be reversed with IV clonidine but could not be reliably precipitated with IV naloxone.

Animals↗
PubMed1982

Concurrent measurement of solvent vapor concentrations and effects on operant behavior using a dynamic exposure system.

A method is described for exposing mice, lever-pressing on an operant schedule for water reinforcement, to continuously-generated solvent vapors. Concurrent monitoring of chamber concentration and schedule-controlled behavior allows a correlation of the magnitude and time course for behavioral effects with changes in the levels of solvent exposure. Data are presented showing the acute effects of 1,1,1-trichloroethane over the range of 1000-8000 ppm on behavior maintained by a fixed-ratio 100 schedule of water presentation. Concentration-dependent decreases in response rates with a rapid onset and recovery were obtained.

Animals↗
PubMed1982

Intravenous buspirone self-administration in rhesus monkeys.

Rhesus monkeys trained to press levers for intravenous cocaine injections were tested with saline and various doses of buspirone, chlordiazepoxide, and clorazepate. Buspirone was not self-administered at rates significantly above saline control levels. Chlordiazepoxide and clorazepate also failed to serve as reinforcers under these conditions. The lack of reinforcing properties, taken together with the results of other preclinical behavioral studies, suggests a low potential for recreational use of buspirone in man.

Animals↗
PubMed1982

Unlimited access intravenous drug self-administration in rhesus monkeys.

Rhesus monkeys implanted with intravenous catheters readily self-inject a wide variety of psychoactive drugs. Under conditions where access to drug is not limited, pharmacological variables are important determinants of the rate and pattern of drug-reinforced responding. Data for unlimited access phencyclidine self-administration are presented to illustrate the types of findings obtained from unlimited access studies. The results with phencyclidine indicate a pattern of drug intake that progressed from variable day-to-day response rates at a low dose to relatively stable daily response rate with greater drug intake at a higher dose. The pattern of responding, toxicity, and development of physical dependence seen in these subjects were similar in many respects to results found with several other drugs under conditions of unlimited access. These findings demonstrate that unlimited access studies are particularly useful for revealing toxic consequences of self-administered doses. Moreover, a review of the literature indicated that procedures allowing unlimited access by drug-naive monkeys were at least as likely to reveal reinforcing properties of drugs as limited access procedure using drug-experienced subjects.

Animals↗
PubMed1981

Effects of antipsychotic compounds in rhesus monkeys given a choice between cocaine and food.

Chlorpromazine (CPZ) and haloperidol (H) have been suggested as possible antagonists of the reinforcing effects of psychomotor stimulant drugs. To test this hypothesis in animals, four rhesus monkeys were trained in a preference procedure to choose between intravenous injections of cocaine or food presentation. Frequency of cocaine choice increased as unit dose of cocaine was increased. Continuous infusions of low or intermediate doses of CPZ or H either did not affect or increased the frequency of cocaine choice. Higher doses of CPZ or H completely suppressed responding for both reinforcers. Although ther appears to be a mutual antagonism of some of the effects of cocaine and these antipsychotic compounds, the results of the present experiment fail to support the hypothesis that the reinforcing effects of cocaine can be antagonized with CPZ or H.

Animals↗
PubMed1981

Effects of combinations of phencyclidine and pentobarbital on fixed-interval performance in rhesus monkeys.

The effects of phencyclidine (PCP, 0.1-.08 mg/kg), pentobarbital (PB, 2-32 mg/kg) and of combinations of these two drugs were determined in rhesus monkeys trained to respond on a fixed-interval 5-min schedule of food presentation. When combinations of PCP and PB were tested, dose-effect functions for PB on overall response rate were shifted to the left relative to those for PB given alone. This effect was dependent on PCP dose: the higher dose of PCP (0.2 mg/kg) shifted the PB dose-effect function further than did the lower dose (0.1 mg/kg). The effects of both drugs alone and in combination depended upon the rate of responding under control conditions. Individual drugs and combinations increased low rates of responding, increasing and then at higher doses decreased intermediate rates of responding and only decreased high rates of responding. Nevertheless, the effects of combinations of PCP and PB were always shifted to the left relative to PB given alone. This interaction was quantified by using isobolograms for those dependent measures that were decreased by the two drugs given alone or in combination. This analysis revealed that the nature of the interaction between PCP and PB depended upon the dose combination and the measure of performance. Relative to the predictions of a dose-addition model, the interaction was quantitatively greater (additive or supra-additive) when the lower dose of PCP was combined with PB.

Animals↗
PubMed1980

Continuous-access phencyclidine self-administration by rhesus monkeys leading to physical dependence.

IV phencyclidine (PCP) self-administration was studied in five rhesus monkeys. The animals were given 23 h per day access with each respose producing an injection. For the first seven sessions saline was made contingent on responding. For the next 30 sessions responses produced 0.01 mg/kg PCP and for the next 20 sessions responses produced 0.05 mg/kg PCP. Withdrawal signs and symptoms were evaluated every 4 h during the subsequent saline-access period. All animals responded for 0.01 mg/kg injections at rates higher than their initial saline rates. Response rates decreased but total PCP intake increased during access to the higher dose. The levels of PCP self-administered resulted in severe intoxication. Evidence for physical dependence development was obtained. The symptoms emerged within 4--8 h after access was terminated, peaked at 12--16 h, and subsided by 24--48 h. The syndrome could be reversed by IV PCP administration. The most common symptoms were vocalizations, hyperresponsivity, bruxism, oculomotor hyperactivity, and diarrhea. During withdrawal the animals refused preferred food. In some of the animals piloerection, tremors, ear and facial twitches, and priapism occurred. Rhythmic abdominal contractions and emesis were seen in one subject and convulsive activity was seen in one subject.

Animals↗
PubMed1980

Modification of the behavioral effects of phencyclidine by repeated drug exposure and body weight changes.

In the first experiment, the effects of phencyclidine (PCP) on intake of sweetened condensed milk by rats were compared before and during a period of repeated daily injections of PCP or saline. A shift to the right in the PCP dose-effect function was found in rats receiving daily PCP injections indicating tolerance development to the effects of PCP on milk intake. The dose-effect function of PCP was shifted to the right in animals receiving daily saline as well. However, when body weight changes were controlled for in this groups of animals, the effects of PCP were the same as they had been initially, implicating body weight as a determinant of the behavioral effects of PCP. In the second experiment, a direct comparison of the behavioral effects of PCP in high- and low-weight animals revealed diminished effects of PCP in high-weight animals. When these animals were treated with 3H-PCP, brain total radioactivity as well as 3H-PCP in the high-weight animals were significantly lower than those in the low-weight animals.

Animals↗