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W L Woolverton

Publications and source records attributed to W L Woolverton.

136 records · Page 8Linked to original sources
PubMed1980

Structure-activity relationships among some d-N-alkylated amphetamines.

d-N-Alkylated amphetamines were synthesized in a series up to and including d-N-butylamphetamine and potencies of these compounds were compared in (1) rhesus monkeys allowed to respond for intravenous infusions of the drugs, (2) rats allowed to drink a milk solution for 15 minutes each day and (3) isolated, spontaneously beating guinea-pig atria. In the self-administration procedure, d-amphetamine (A), d-N-methylamphetamine (NMA), and d-N-ethylamphetamine (NEA) were self-administered above saline levels at two or more doses by all animals. For these three drugs, maximal response rates were found at similar doses in all animals. However, maximal rates were generally higher in animals maintained on pentobarbital than in animals maintained on cocaine under control conditions. d-N-propylamphetamine (NPA) was self-administered above saline levels by three of four animals at one or more doses. Maximal response rates for NPA were about 1/2 of that of A, NMA and NEA, and the dose-response curve was shifted to the right of these compounds by about 4 times. d-N-butylamphetamine (NBA) maintained responding above saline levels at two doses in only one of three animals. In rats, all of the compounds decreased milk intake in a dose-related manner. A, NMA and NEA were equipotent in disrupting intake, while NPA and NBA were, respectively, 1/4 and 1/6 as potent as the shorter-chain compounds. With the exception of NBA, all compounds increased the rate of beating of the guinea-pig atrium over the range of concentrations tested. In general, for substituents larger than ethyl, potency of d-N-alkylated amphetamines was inversely related to N-alkyl length.

Animals↗
PubMed1979

Tolerance to the behavioral effects of phencyclidine: the importance of behavioral and pharmacological variables.

The effects of phencyclidine (PCP) on the behavior of rats responding to a fixed-interval 1 min schedule of water delivery were determined before, during, and after a period of daily PCP injections. The effects of acute PCP on overall response rate were biphasic: low doses increased and high doses decreased rates. In addition, PCP produced a dose-related decrease in quarter-life and high doses of PCP decreased the number of reinforcers delivered. During the daily injection regimen roughly a two-fold tolerance developed to the effects of 8.0 mg/kg PCP on response rate in animals receiving either presession or post-session injections of this dose, emphasizing the predominance of pharmacological variables in PCP tolerance. However, slight differences between these groups in tolerance development and in the rate of tolerance loss demonstrate that behavioral variables can influence tolerance to the behavioral effects of PCP.

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↗
PubMed1978

Effects of repeated administration of cocaine on schedule-controlled behavior of rats.

The effects of cocaine (4.0--32 mg/kg) on schedule-controlled behavior of rats were determined before and during a period of repeated administration of cocaine. In rats trained to lever press on a fixed ratio 40 schedule for food delivery, cocaine (8.0--32 mg/kg) initially decreased response rate in a dose-related manner. During the period of repeated administration, the effects of cocaine on response rate and running rate were attenuated in 2 rats and did not change in 2 others. When dose-effect functions of cocaine were redetermined, a shift to the right was observed in several measures indicating the development of tolerance to these effects of cocaine on performance. In rats trained to lever press on a DRL 20" schedule for food delivery, cocaine (4.0--32 mg/kg) increased response rates, decreased number of reinforcements per session and shifted interresponse time distributions to the left (shorter IRT's in all rats). During the period of repeated administration, the effects of the daily dose of cocaine (16 mg/kg) on all these measures were attenuated. Tolerance to cocaine was further indicated by a shift in the dose effect function of cocaine to the right during the redetermination.

Animals↗
PubMed1978

Cocaine as a discriminative stimulus for responding maintained by food in squirrel monkeys.

Squirrel monkeys were trained in a choice procedure to discriminate a dose of 100 micrograms/kg cocaine from saline. Following an injection of cocaine, responding on the right lever was reinforced with food, whereas following an injection of saline, responding on the left lever was reinforced with food. A high degree of stimulus control (100% correct) was established within 20 experimental sessions. The dose-response function of cocaine on lever choice was then determined. When intermediate doses (10, 25 and 50 micrograms/kg) were administered prior to test sessions, a dose-dependent generalization decrement was seen. One monkey was found to discriminate as low as 25 microgram/kg cocaine from saline.

Animals↗
PubMed1978

Tolerance and cross-tolerance to cocaine and d-amphetamine.

The effects of cocaine (4.0-32 mg/kg) and d-amphetamine (0.5-4.0 mg/kg) on milk intake of rats were determined before and during periods of repeated daily administration of each drug. Experimental sessions consisted of 15 minutes access to 50 ml of a sweetened condensed milk solution. After the determination of the disruptive effects of single injections of cocaine or d-amphetamine on milk intake, rats were injected daily with either 16 mg/kg of cocaine 15 minutes before the session, 16 mg/kg of cocaine immediately after the session, 2.0 mg/kg of d-amphetamine 15 minutes before the session or saline before the session. During the period of repeated administration when milk intake had stabilized in each group, dose-effect functions for cocaine and d-amphetamine on milk intake were redetermined. On selected days, test doses of either drug were substituted for the usual daily injection. Test doses were separated by at least 3 days of stable intake after injection of the appropriate drug or saline. During the period of repeated administration, milk intake returned toward control levels for animals receiving daily cocaine or daily d-amphetamine before the session. Further, when the dose-effect functions for cocaine and d-amphetamine on milk intake were redetermined, a shift to the right (i.e., toward larger doses) was observed in all groups that had received drug presession during the repeated administration. This indicates that the animals became tolerant to cocaine and d-amphetamine as well as cross-tolerant to both drugs. The development of tolerance to cocaine was contingent upon the relationship of the time of injection to milk availability. Animals that had received postsession injections of cocaine during repeated administration were more sensitive to the effects of cocaine and d-amphetamine on milk intake.

Animals↗