Endogenous opiates: 1979(1).
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Biomedical subjects
Publications and source records attributed to G A Olson.
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Twenty-four male albino rats were given daily intraperitoneal injections of vasoactive intestinal polypeptide (VIP), motilin, human gastrin I (1-17) or the diluent control vehicle at a dose of 100 micrograms/kg for four consecutive days and food intake, water intake, body weight, and running wheel activity were determined every 24 hours. Animals injected with motilin or human gastrin I (1-17) exhibited decreased food intake relative to those injected with VIP or diluent, which did not differ from each other, although food intake increased reliably over days. The mean water consumption followed the same pattern as that of food intake. As expected from the above results, VIP produced weight gains as compared with rats injected with motilin or gastrin but not reliably more than after diluent. A reliable effect of trials for weight gain was the greatest on day three. Running wheel activity was not affected by injections of human gastrin I (1-17), motilin, or diluent but was reliably decreased by VIP. No significant differences existed across days. Although the results indicate that GI peptides may affect behavior when injected systemically and that like other peptides they have multiple effects, caution is urged in the interpretation of behavioral results at this time.
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Pregnant Rhesus monkeys were infected via instillation of influenza, mumps and western equine encephalomyelitis viruses respectively into the amniotic sacs at approximately 90 days gestation to determine if fetal infections would occur. Virus was recovered from fetal tissues after seven days in 100% of the exposed animals. Thus, the viruses are capable of causing fetal infection. Rhesus monkey fetuses were inoculated with influenza, mumps and WEE viruses by the direct intracerebral route at approximately 90 days gestation to determine possible teratogenicity of the viruses. influenza virus caused no malformations or measurable fetal effects. Mumps virus resulted in significant fetal mortality. WEE virus resulted in a 100% incidence of encephalitis and hydrocephalus. Thus, mumps and WEE viruses are teratogens in primates and are potential teratogens of man.
Facilitation of the learning of a discrimination reversal task for a reward of food was found in rhesus monkeys after subcutaneous administration of a potent pentafluorinated enkephalin analog. (D-Ala2)-F5-Phe4-enkephalin-NH2. General activity, short-term memory, startle, and analgesia, however, were not significantly affected. In a within-subject design, each of 6 monkeys (3 males and 3 females) received each of 5 doses of the enkephalin analog (0.1, 1, 10, 100, and 1,000 microgram/kg). One daily injection was made for 7 consecutive days, including pre- and posttests on the first and last days with the diluent control. The enkephalin doses, with the exception of the 0.1 microgram/kg level, produced significantly faster learning than the diluent. Some sex differences were suggested by the data, but these effects are difficult to interpret. The results suggest that relatively small amounts of this analog given systematically can exert a reliable effect on a complex behavior such as reversal learning at doses devoid of opiate effects, due perhaps to enhanced cognitive flexibility rather than improvement in short-term memory or association formation.
Chickens were tested in a tonic immobility paradigm after a single intraperitoneal injection of either 0.0, 0.1, 1.0, 10.0; 100.0, or 1000.0 microgram/kg of the potent opiate analog, (D-Ala2, F5Phe4)-Met-enkephalin-NH2. An inverted-U relationship was obtained, with 100 microgram/kg being the most effective in prolonging immobility. This dose was used in subsequent studies involving pretreatment with naloxone or diluent followed by treatment with diluent, (D-Ala2, F5Phe4)-Met-enkephalin-NH2 (a strong opiate), or (D-Phe4)-Met-enkephalin (a weak opiate). The results indicated that although naloxone had mixed effects in attenuating the duration of tonic immobility, even the analog with negligible opiate activity reliably potentiated the response. Therefore, a component of the effect of opiate peptides on tonic immobility could be due to a non-narcotic action.
Intraperitoneal injections of naloxone hydrochloride (1, 2, 4, and 8 mg/kg) suppressed food intake in both normal and hypothalamic obese rats maintained on a 4-hr per day feeding schedule. The decrease in feeding was more pronounced in the animals with ventromedial hypothalamic lesions. Appetitively motivated feeding, i.e., the consumption of sweetened milk under nondeprived conditions, was also suppressed by naloxone, but there was no reliable difference between groups. It is concluded that opiate receptors located in the ventromedial hypothalamus are not essential for the effects of opiate agonists and antagonists on feeding behavior.
The discovery of receptors in the brain for opiates and the structure of the endogenous peptides for these receptors has led to an explosion of interest in this field. The present review is the first of an annual series. It summarizes many of the highlights of research with opiate peptides published with a date of 1978 or earlier.
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1) Immunization of rats with dextran receptors appears to confer resistance to development of caries. 2) A significant negative correlation between antiserum titers and caries scores is observed in immunized rats. 3) Antiserum specific for dextran receptors does not inhibit in vitro adherence of live bacteria in sucrose supplemented media. 4) Free receptors can bind to dextran, thereby inhibiting its ability to induce bacterial agglutination.
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The general activity level of a goldfish is easily monitored by placing it in water to a depth of 2.5 cm in an aquarium on top of an activity meter. With this system, goldfish were administered a 5 microliter (80 microgram/kg) intracranial (IC) or intraperitoneal (IP) injection of one of 21 compounds and tested for general activity. The results indicated that activity decreased significantly over time and the peptides differentially decreased activity, with the greatest alterations in activity produced by two new enkephalin analogs: D-Ala2, F5Phe4-enkephalin-NH2 and Nalpha Nepsilon-bis-(D-Ala2-enkephalin)-Lys-NH2. Overall, decreased activity began approximately 3 min after an IC injections and 6 min after an IP injection. The longer latency after IP injections may indicate the time required for the substance, either in its original or fragmented form, to reach and cross the blood-brain barrier and makes a primary peripheral effect unlikely. Most of the peptides or possibly their metabolites appeared to enter the brain since no significant difference in activity existed after IC and IP injections, with both producing reliable decreases from the control. In summary, peptides can exert behavioral effects after both IC and IP administration in goldfish.
The effects of D-Ala2-beta-endorphin administered either intravenously (IV) or intracisternally (IC) in squirrel monkeys were tested using a number of behavioral measures: general activity, eating, social behavior, aggression/distress, analgesia, and startle/escape. There were 10 groups (N = 5) consisting of 4 dose levels administered IC (0.4, 40, 400 microgram/kg) and 6 dose levels injected IV (0, 4, 40, 80, 400, 800 microgram/kg). Every monkey was tested with all tasks on each of 5 identical repeated trials, one pre-injection baseline trial and 4 post-injection trials. After IC administration, the 2 largest doses exerted toxic effects, which were partially reversed with naloxone, producing in 2 cases muscular rigidity and profound sedation. The smaller 4 microgram/kg dose produced significant decreases in activity over trials but increased reactivity to noxious stimulation after the initial post-injection trial. With IV injection reliable changes in activity and approach to food were found. The results demonstrate significant behavioral effects of an endorphin analog in the squirrel monkeys after both central and peripheral injection.
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Oral secretions were collected from 100 human volunteers, concentrated, and assayed for their ability to inhibit glucan-dependent adherence of S mutans strains to glass. Some samples were found to contain adherence inhibition activity. The inhibitor was heat labile and nondialyzable but dependent on the presence of a dialyzable molecule. Comparison of activities with the caries experience (DMFT) showed that individuals with the highest activity had significantly lower mean caries scores, but that cariesfree donors did not differ significantly from caries-positive donors in mean adherence inhibition activity. These results suggest that some persons may have substances in their oral secretions that play a role in resistance to dental caries.
Several methods for external sampling of blood and administration of intravascular fluids are applicable to reptilian species. This paper reviewed some of the technics that have been previously reported and introduced several new procedures applicable to snakes, turtles, alligators, crocodiles, and lizards.
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