Biomedical subjects
Publications and source records attributed to J R Weeks.
Infusion of fluids into unrestrained animals requires the use of a flow-thru swivel. A method is described for the construction of a simple efficient swivel assembled from disposable plastic syringes and needles.
Interactions of prostaglandin E1 (PGE1) with morphine have been reported in several test systems and an hypothesis has been advanced for a role of prostaglandins in morphine analgesia and physical dependence. In rats self-administering morphine intravenously, a simultaneous and continuous infusion of naloxone hydrochloride at 56 to 560 mug/kg/day caused the expected increase in injection rate for morphine. Infusion of PGE1 by itself at 56 or 180 mug/kg/day had no effect on the rate of morphine intake. Likewise the addition of PGE1 at 180 mug/kg/day did not potentiate the increase caused by naloxone (56 or 180 mug/kg/day) when it was added to the naloxone infusion. These results do not support a role for prostaglandins in the behavioral aspects of morphine addiction. However, larger doses of PGE1 (1 and 1.8 mg/kg/day), which were without overt effects in normal rats, caused severe and incapacitating prostration in morphinized rats.
The prostaglandins have diverse cardiovascular effects, differing not only among themselves but also according to the organ affected and the species. Some of the pharmacological actions of the prostaglandins may have practical application in hypertensive crises, shock, peripheral vascular disease, and to maintain the patency of the ductus arteriosus in congenital heart malformations. They may play physiological roles as locally produced modulators or regulators of kidney function and blood flow to specific organs or tissues. Such roles are yet to be firmly established.
In a number of assay systems, some 17-phenyl-trinor-prostaglandins were similar in activity and potency to the corresponding parent prostaglandin. In others, the 17-phenyl analogs appeared several times more potent. In the hamster antifertility assay, which is considered to measure luteolytic activity, 17-phenyl-18,19,20-trinor prostaglandin F2alpha was about 90-times PGF2alpha in potency. Rat blood pressure responses to 17-phenyl analogs were significant. The 17-phenyl-trinor PGF2alpha pressor potency was 5 times that of PGF2alpha. The 17-phenyl-trinor PGE2 blood pressure response was atypical since a pressor rebound phenomenon followed the expected depressor response. Lastly, 17-phenyl-trinor PGF2alpha was more potent than PGF2alpha in synchronizing the estrous cycle in beef cows.
Drug self-administration studies in animals have generally used drugs that are abused by man. The oral route by adding drug to the drinking water is simple, but the bitter taste of many drugs requires that the animals first be forced to consume treated water. The intravenous route, wherein relatively unrestrained rats or monkeys press a lever to obtain intravenous drugs, permits precise control over the dose and can be readily adapted to schedules and manipulations customarily used in the behavioral sciences. Environmental factors affecting drug intake include the dose its schedule of administration, and conditioning of drug administration to secondary cues. There are differences in drug self-administration of stimulant drugs (as amphetamines) and depressants (as morphine and barbiturates). There is an inverse relation between the size of the dose and number of injections taken, but for stimulants daily intake will remain constant whereas for depressants smaller doses are only partially compensated for by increased numbers of injections. Likewise, drug intake of stimulants is better maintained on ratio schedules. Neutral stimuli, as lights or buzzers, paired with drug injections can be used to elicit conditioned responses. Such responses have been used to evaluate the reinforcing properties of drugs.
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