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C P Cramer

Publications and source records attributed to C P Cramer.

28 records · Page 2Linked to original sources

Ethylketocyclazocine and bremazocine analgesia in neonatal rats.

In three experiments we examined the analgesic potency of kappa opioid receptor agonists in 2- and 16-day-old rats. Ethylketocyclazocine (1-50 mg/kg) produced similar dose- and time-dependent increases in the latency to retract a hind paw from a noxious thermal stimulus in rats of both ages. Bremazocine (0.001-10 mg/kg), a kappa agonist with reported antagonist activity at mu receptors, was also effective in producing analgesia in 2-day-old rats. The dose-effect relationship for bremazocine was nonmonotonic. Bremazocine analgesia (0.1 mg/kg) was reversed by both naltrexone and MR2266, a putative kappa opioid antagonist. These results are discussed in terms of the functional integrity of a kappa analgesic system in the developing rat.

Analgesia↗

The ontogeny of opiate tolerance and withdrawal in infant rats.

The acquisition of morphine analgesic tolerance was investigated in neonatal rats. Morphine was found to produce a potent analgesia, as measured by latency to retract a hindpaw from a 52 degree C hotplate, in rat pups as young as 1 day of age. Morphine analgesic tolerance, however, did not develop in rats until the third week of life. Rats given the same daily morphine regimen starting at 15 days of age or older showed rapid tolerance development. The data from four experiments indicate that experience with morphine prior to this age (Day 15) does not impact on the analgesic efficacy of the drug. Similarly, when morphine treatment was discontinued and the rats given a naloxone challenge, withdrawal symptoms were not observed in very young rats. Opiate withdrawal was first detected in rats that started their daily morphine treatment at 30 days of age and were then challenged with naloxone at 52 days of age. Therefore, two correlates of opiate addiction, tolerance and withdrawal, appear to be relatively late-developing phenomena in the rat.

Age Factors↗

Nutritive and nonnutritive determinants of milk intake of suckling rats.

In order to determine the factors that enhance milk intake during deprivation, albino rats 15, 20, and 25 days of age were subjected, for 8 hr, to one of the following regimens: (1) privation, that is, separation from the dam and food; (2) privation with a maternal, thelectomized female; (3) privation with a maternal female whose nipples had been surgically ligated; (4) separation from the dam and food but receiving three 2% body weight intragastric preloads of milk; (5) with a dam whose nipples had been ligated and receiving the same intragastric preloads as Group 4; and (6) nondeprived rats. Rats were then allowed 45 min to suckle an anesthetized dam that was induced to let down milk every 4 min by intravenous oxytocin infusion. Intake at Day 15 was reduced by the opportunity to suckle, independent of receiving a milk load. This same trend was apparent, although not as strong, among Day 20 rats. By Day 25, nonnutritive suckling during the privation period no longer attenuated milk intake, although preloads did, whether or not they were paired with nonnutritive suckling. Thus, suckling in albino rats becomes increasingly freed from oral demands and more responsive to the nutritive consequences.

Aging↗

Transitions in the dehydration-induced inhibition of milk intake in suckling rats.

The effects of acute cellular or extracellular dehydration on milk intake via suckling were determined in rats 5, 10, 15, and 20 days of age. Milk was made available 10 times to each rat pup by the intravenous infusion of oxytocin to anesthetized test dams. Prior to 15 days of age, milk intake was not affected by either intracellular or extracellular dehydration. In rats 15 days and older, however, both forms of dehydration reduced milk intake at the nipple. Thus, dehydration starts to inhibit suckling behavior at the onset of weaning, when food and water are both taken directly from the environment by the developing animal.

Animals↗

Mechanisms of control of milk intake in suckling rats.

To reconcile reported differences in the development of internal controls over milk intake via suckling, infant rats 5-20 days of age were allowed to withdraw milk from anesthetized dams periodically induced to let down milk by intravenous infusion of oxytocin. In experiment 1, milk supply was made unlimited by providing pups with a series of milk-replete dams. Five- and ten-day-old pups withdrew inappropriately large volumes of milk, whereas 15- and 20-day-old pups limited intake to moderate volumes. In experiment 2, intake of deprived and nondeprived pups was measured after only 10 oxytocin-induced milk letdowns, comparable to the normal nursing bout. When milk availability was thus limited, pups of all ages consumed volumes of milk dependent on their level of deprivation. Moreover intake of pups 10-20 days of age was highly correlated with incidence of nipple shifting. Thus rats as young as 5 days of age can vary the rate at which milk is taken from a limited source; however, not until 15 days are they able to control the volume withdrawn from an unlimited source.

Aging↗

The contribution of ambient temperature to suckling behavior in rats 3-20 days of age.

To assess the role of ambient temperature on the expression of adultlike control over suckling behavior of infant rats, preweanling pups were tested for nipple attachment and milk intake while suckling in either room temperature (25 degrees C) or nest temperature (34 degrees C). In one experiment, attachment latency was measured following 1, 4, or 24 hr of deprivation at 3, 6, 9, 12, or 15 days of age. Latency was generally reduced by testing in high ambient temperature. Increasing deprivation reduced latency at all ages. Elevated temperature, however, did not accentuate deprivation-dependent differences. In a 2nd experiment, milk intake via a posterior tongue cannula was measured in pups 5, 10, 15, or 20 days of age, suckling at either room or nest temperature. Environmental temperature did not significantly affect intake at any age. These data eliminate ambient temperature as a critical factor for adultlike control of suckling behavior in infant rats.

Age Factors↗

The ontogeny of nipple-shifting behavior in albino rats: mechanisms of control and possible significance.

Nipple-shifting behavior was studied in rats 3--30 days old in 4 experimental paradigms. The incidence of nipple-shifting of rats tested in groups of 3 on their nonlactating, anesthetized mother was age-related. Rats 12 days of age and younger did not leave the nipple first suckled during the 2-hr test period. Starting by Day 15, however, nipple-shifting increased and reached its maximum in 24-day-old rats. This behavior's incidence was directly related to maternal (and, therefore, nutrient and water) deprivation (Experiment I). Milk letdown reduced the incidence of nipple-shifting behavior at all ages studied and synchronized its occurrence, as almost all shifts occurred immediately aftet letdown and almost none during the 15-min interval between successive milk letdowns (Experiment II). Testing rats individually on the nonlactating, anesthetized mother produced age-related effects. Shifting was virtually eliminated in 15-day-old rats, markedly reduced in 21-day-old rats, and not affected in 27-day-old rats tested individually (Experiment III). Rats 27 and 30 days of age, upon leaving a nipple, ate and did not return to suckle. Rats 15 days old never ate and always returned to suckle (Experiment IV). Twenty-one-day-old rats suckled, and many ate in the mother's presence. The significance of these findings relates to maximizing milk intake and facilitating the process of weaning.

Aging↗

Regulation by the pituitary gland of circadian rhythms in the hamster.

Locomotor activity of male hamsters was recorded during long-term exposure to constant light (LL), constant darkness (DD) and during entrainment (modification of a circadian rhythm) to a 14 h light : 10 h darkness photoperiod (14L : 10D). In LL the period of the activity cycle was substantially longer in hypophysectomized than in control animals. This difference persisted during tests in DD. Although hypophysectomy reduced the duration of the active phase in some hamsters, overall the difference between the groups was not significant. The phase angle of onset of activity in 14L : 10D was not affected by hypophysectomy. Hypophysectomized female hamsters tested in DD had activity rhythms whose periods were longer than those of control animals; they were also significantly less active than corresponding controls during the first 4 h of the subjective night but the duration of the active phase did not differ significantly between the groups. These results suggest that hormones of the pituitary-gonadal axis modulate the period of circadian oscillation.

Activity Cycles↗

Oxytocin and vasopressin hexapeptide fragments have opposing influences on conditioned freezing behavior.

We investigated the influence of C-terminal fragments of oxytocin (OT) and arginine vasopressin (AVP) on conditioned freezing behavior. Subcutaneous injections of 0.3 microgram AVP(4-9) or OT(4-9) given to rats after shock training or before behavioral observation significantly altered fear-induced freezing behavior. Animals treated with OT hexapeptide froze less than controls, while animals treated with AVP hexapeptide froze more. These results support the concept that the hexapeptide metabolites of oxytocin and vasopressin can selectively modulate certain behavioral processes, and that these peptides have opposite effects on performance in behavioral tests designed to evaluate memory consolidation and retrieval.

Animals↗