Interaction of carboxysalsolinol with the ethanol discriminative stimulus.
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Alcohol Drinking↗
Biomedical subjects
R E Chipkin
Publications and source records attributed to R E Chipkin.
In vitro activities of some synthetic substance P analogs.
Substance P (SP) and several analogs and fragments have been synthesized and evaluated on non-stimulated and stimulated guinea-pig ileum. In the former test system the potency order was as follows: SP(4--11) greater than SP = [Tyr7]-SP = [Eth11]-SP = [Nle11]-SP greater than [Dala9]-SP greater than SP(7--1) = [Tyr7]-SP(7--11) greater than [Eth11]-SP(7--11) greater than [DAla9]-SP(7--11) greater than [Nle11]-SP(7--11) greater than SP(1--7). The spasmogenic activity of SP and analogs was preserved in the same potency order on stimulated guinea-pig ileum; none of these modifications resulted in an analog with narcotic-like activity. These data are discussed in terms of a hypothetical SP receptor in extravascular smooth muscle.
Animals↗
Substance P and opioid interaction on stimulated and non-stimulated guinea pig ileum.
In the past, substance P (SP) has been suggested to be both an opiate agonist and an antagonist. It therfore seemed appropriate to examine potential interactions of SP and opioids on guinea pig ileum. On non-stimulated ileal strips SP caused a dose responsive increase in contraction. Pretreatment of the tissue with morphine (3, 30, 300, 3000 nM), enkephalin (1.42, 14.2, 142, 1420 nM), naloxone (5nM), or atropine (0.144 micron) did not significantly alter the spasmogenic effect of SP. On stimulated guinea pig ileum, whereas morphine and enkephalin inhibited the electrically induced twitch, SP adminstration resulted in contraction of the tissue. Additionally, neither strongly effective non sub-threshold doses of SP antagonized the effects of the narcotics. These data are discussed in terms of separate receptors mediating the effects of the opiates and SP on guinea pig ileum.
Animals↗
Aversiveness of oral methadone in rats.
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Animals↗
Brief communication. Generalization of [DAla2]-enkephalinamide but not of substance P to the morphine cue.
Rats were trained to discriminate morphine (7.5 mg/kg, IP) from saline in a two bar positively reinforced lever pressing paradigm on a FR4 schedule. Morphine (IP) showed a naloxone reversible dose-related generalization to the training dose. [DAla2]-Methionine enkephalinamide (DAE) at 1 mg/kg and Substance P (SP) at 0.1 and 0.25 mg/kg showed vehicle appropriate responding after IP injection. DAE (5 mg/kg) disrupted responding completely; SP (0.5 and 0.1 mg/kg) disrupted responding in 50% of the rats. The disruption caused by IP injection of DAE was not naloxone reversible. Intraventricular injection of morphine (5 microgram/rat) and DAE (5 microgram/rat) produced generalization to the opiate cue. The effect of DAE was reversed by naloxone (1 mg/kg, SC). SP (500 and 750 ng/rat, IVT) produced saline-like responding; 1 microgram/rat disrupted responding completely. These data demonstrate that morphine and enkephalin, but not Substance P, share similar discriminative properties.
Animals↗
Potentiation of stress-induced analgesia (SIA) by thiorphan and its block by naloxone.
Exposure of rats to inescapable footshock produces an analgesic effect. To determine if endogenously released enkephalins play a role in this phenomenom, rats were treated with the enkephalinase inhibitor thiorphan (T), exposed to inescapable stress, and tested in the tail-flick test for antinociception. T (10-100 mg/kg sc) caused a dose-related potentiation of both the peak effect and the duration of the SIA. This effect was blocked by doses of naloxone (1 mg/kg sc) that did not affect baseline response latencies.
Amino Acids, Sulfur↗
Effect of propranolol on antinociceptive and withdrawal characteristics of morphine.
Propranolol at a dose (10 mg/kg) which did not alter tail-flick latency by itself, did not alter the ED50 of morphine when given 10 min prior to the narcotic. Propranolol at doses of 10 and 25 mg/kg given 10 min prior to naloxone challenge did not significantly alter the frequency of naloxone induced jumping 72 hr after morphine pellet implantation. The ED50 of naloxone in morphine pelleted mice was not altered by treatment with propranolol at 0, 24, and 48 hr after pellet implantation. Naloxone caused hyperactivity in mice when administered 72 hr after morphine pellet implantation. An injection of 25 mg/kg propranolol 10 min prior to naloxone did not block this hyperactivity. In addition, administration of 10 mg/kg of propranolol every 8 hr to rats during withdrawal from morphine failed to alleviate the withdrawal syndrome as evidenced by changes in either body weight or water intake. These data suggest that the beta-adrenergic blocking agent, propranolol, does not alter the antinociceptive activity or lessen the withdrawal syndrome of morphine in rodents.
Analgesics, Opioid↗
Relationship of yeast-injection induced changes in brain met-enkephalin and analgesia.
Subplantar injection of Brewer's yeast induces a hyperalgesia that is associated with an increase in the level of striatal Met-enkephalin (ME); there was no change in the hypothalamus of periaqueductal gray. To test the relationship between striatal ME and analgesia, naloxone (10, 3, 0.5 mg/kg, SC) or thiorphan (100 micrograms, ICV) were administered. Neither drug caused a potentiation or a reduction in the hypersensitivity. These data suggest that an increase in striatal does not result in altered pain sensitivity in this model.
Analgesia↗