Spatial learning in deer mice: sex differences and the effects of endogenous opioids and 60 Hz magnetic fields.

We examined the effects of brief exposure to weak 60 Hz extremely low frequency (ELF) magnetic fields and opioid systems on spatial behavior and learning in reproductive adult male and female deer mice, Peromyscus maniculatus. Sex differences were evident in spatial performance, with male deer mice displaying significantly better performance than female mice in the Morris water maze, whereby animals had to acquire and retain the location of a submerged hidden platform. Brief (maximum 5 min) exposure to weak (100 microT) 60 Hz magnetic fields during task acquisition significantly improved female performance, eliminating the sex differences in acquisition. The opiate antagonist, naltrexone, also improved female acquisition, though significantly less than the magnetic fields. These facilitatory effects involved alterations of "non-spatial" (task familiarization and reduction of related anxiety/aversive related behaviors) and possibly "spatial" aspects of the task. Enhancement of enkephalin activity with the enkephalinase inhibitor, SCH 34826, significantly reduced task performance by male deer mice. Both naltrexone and the 60 Hz magnetic fields attenuated the enkephalin mediated reductions of spatial performance. These findings indicate that brief exposure to 60 Hz magnetic fields can enhance water maze task acquisition by deer mice and suggest that these facilitatory effects on spatial performance involve alterations in opioid activity.

Sex differences in the antinociceptive effects of the enkephalinase inhibitor, SCH 34826.

The effects of endogenous opioid peptides are limited by proteolytic enzymes such as endopeptidase 24.11 ("enkephalinase"), which cleaves the Gly-Phe bonds in Met- and Leu-enkephalin. SCH 34826 [(S)-N-[n-[1-[(2,2-dimethyl-1,3-dioxolan-4- yl)methoxy]carbonyl]-2-phenylethyl]-L-phenyl-alanine-B-alanine] is a potent, highly specific, enkephalinase inhibitor that has marked analgesic effects in laboratory rodents. The present study compared the effects of SCH 34826 on nociception and restraint stress-induced opioid analgesia in reproductive adult male and female deer mice, Peromyscus maniculatus. SCH 34826 had significantly greater antinociceptive actions and facilitatory effects on stress-induced analgesia in male than female mice. These antinociceptive effects of SCH 34826 were reduced by the general opioid antagonist naloxone and completely blocked by the specific delta opioid receptor antagonist, ICI 174,864, and nonsignificantly affected by the mu and kappa opioid receptor antagonists, beta-funaltrexamine and nor-binaltorphimine, respectively. These results show that there are sex differences in the effects of the enkephalinase inhibitor, SCH 34826, on opioid-mediated antinociception and that these sex differences are associated with delta opioid mechanisms.

Sex differences in naloxone- and Tyr-MIF-1-induced hypoalgesia.

Reproductive adult male and female deer mice that received daily (7 days) injections of either the prototypic exogenous opiate antagonist, naloxone (1.0 mg/kg), or the endogenous putative antiopioid tetrapeptide, Tyr-MIF-1 (Tyr-Pro-Leu-Gly amide; 1.0 and 10 mg/kg), followed by determinations of thermal nociceptive sensitivity (hot-plate response) developed hypoalgesia. There were significant sex differences in this opioid blockade-induced or associated analgesia, with male mice displaying significantly greater hypoalgesia than females. Mice that received daily injections of either naloxone or Tyr-MIF-1 for 7 days without any accompanying determinations of nociceptive sensitivity (days 2-6 of treatment) failed to show any hypoalgesia on day 7 when they received the antagonist followed by a measurement of nociception. These results indicate that there are sex differences in both naloxone- and Tyr-MIF-1-induced hypoalgesia, and suggest that this pattern may be associated with sexually dimorphic opioid modulation of aversive conditioning.

Sex differences in the effects of Tyr-MIF-1 on morphine- and stress-induced analgesia.

There is evidence suggesting that the endogenous tetrapeptide, Tyr-MIF-1 (Tyr-Prol-Leu-Gly-amide), has antagonistic or modulatory effects on opioid-mediated analgesia. There is also substantial evidence for sex differences in opioid effects, whereby male rodents display greater levels of opioid-mediated analgesia than females. In the present study, determinations were made of the effects of Tyr-MIF-1 on morphine- and restraint stress-induced opioid analgesia in adult male and female deer mice, Peromyscus maniculatus. Intraperitoneal treatment with Tyr-MIF-1 (0.10-10 mg/kg) reduced morphine- and stress-induced analgesia in both male and female mice, with Tyr-MIF-1 having markedly greater antagonistic effects in male than female mice. These results indicate that there are sex differences in the modulatory (antiopiate) effects of Tyr-MIF-1 on opioid-mediated analgesia.

Developmental changes in opiate-induced analgesia in deer mice: sex and population differences.

We examined developmental changes in nociception and mu (morphine) and kappa (U-50,488) opiate-induced analgesia in male and female deer mice of two different populations; Peromyscus maniculatus artemisiae from a mainland region and P. m. angustus from a small island. Both populations displayed significant developmental changes in nociception and morphine (10 mg/kg) and U-50,488 (10 mg/kg)-induced analgesia. Basal thermal response latencies (nociceptive responses) and the levels of mu and kappa opiate-induced analgesia increased over 14-35 days of age, with maximum analgesic responses in adults (35+ days of age). In both of the populations, young (neonatal-weaning) male mice displayed significantly higher thermal response latencies and greater levels of naloxone (1.0 mg/kg) antagonized opiate-induced analgesia than young females. There were also population differences in the levels of analgesia, the insular mice displaying greater mu and lower kappa opiate-induced analgesic responses than the mainland animals. The population differences in mu and kappa opiate-induced analgesia were evident in young and adult mice of both sexes. These results show that there are significant sex and population differences in nociception and opiate-induced analgesia in young (neonatal-weaning) and adult deer mice.

Population differences in benzodiazepine sensitive male scent-induced analgesia in the deer mouse, Peromyscus maniculatus.

We compared opioid and nonopioid involvement in the mediation of scent-induced analgesia in two populations of deer mice, Peromyscus maniculatus; P. m. artemisiae from a mainland region and P. m. angustus from a small marine island. Exposure to bedding taken from the soiled home cage of an isolated (dominant aggressive) male resident elicited a significant increase in the nociceptive responses of male deer mice from mixed sex pairs, with the island population of mice displaying significantly greater analgesic responses than the mainland animals. In the mainland population of mice, the large amplitude analgesia induced by the scent of a conspecific was insensitive to the opiate antagonist, naloxone, but could be blocked by either the benzodiazepine antagonist, Ro 15-1788, or agonist, diazepam. Exposure to the scent of individuals from the island population elicited a lower amplitude analgesia that was sensitive to both the opiate and benzodiazepine manipulations. In the island population, both the lower amplitude analgesia induced by the scent of a conspecific and the higher amplitude analgesic elicited by the scent of a mainland animal was blocked by naloxone and only partially reduced by the benzodiazepine manipulations. Bedding treated with the peppermint also induced analgesia, with the island mice displaying a markedly greater analgesic response than the mainland animals. In both populations of deer mice the peppermint-induced analgesia was blocked by naloxone and insensitive to the benzodiazepine manipulations. These findings are considered in terms of their possible ecological significance and relations to the differences in agonistic and social behaviors between island and mainland populations of deer mice and other small rodents.

Novelty-induced opioid analgesia in deer mice (Peromyscus maniculatus): sex and population differences.

Exposure to a new environment elicited significant, naloxone (1.0 mg/kg) reversible analgesic responses in three different populations of deer mice; Peromyscus maniculatus artemisiae from the mainland, and P. m. angustus and P. m. triangularis from small marine islands. In all cases male deer mice displayed significantly greater levels of analgesia than females. In addition, the levels of analgesia were significantly greater in the insular than in the mainland populations. These results indicate that there are substantial sex and population differences in the novelty-induced analgesia displayed by natural and laboratory populations of deer mice.

Male scent-induced analgesia in the deer mouse, Peromyscus maniculatus: involvement of benzodiazepine systems.

Exposure to bedding taken from the soiled home cage of an isolated male resident elicited a significant increase in the nociceptive responses of male deer mice, Peromyscus maniculatus artemisiae, from mixed sex pairs. The analgesia induced by exposure to the male scent was insensitive to the opiate antagonist, naloxone, and was blocked by either pre- or post-olfactory exposure injections of the benzodiazepine antagonist, Ro 15-1788, or agonist, diazepam. This non-opioid analgesia was of brief duration (15-30 min) and rapid onset, being evident after 1 min of exposure to the olfactory cues. Bedding treated with the novel odor of peppermint also induced analgesia in the deer mice. This analgesia was opioid mediated, being blocked by naloxone and insensitive to the benzodiazepine manipulations. Exposure to either fresh bedding, or the soiled bedding of another mixed sex pair of deer mice, had no significant effect on nociception. These results indicate that exposure of male deer mice to the olfactory cues associated with a potentially threatening individual (dominant/aggressive isolated male) elicits an analgesic response that involves alterations in the activity of benzodiazepine systems.

Sex and day-night differences in opiate-induced responses of insular wild deer mice, Peromyscus maniculatus triangularis.

We examined the effects of mu and kappa opiate agonists on the day- and night-time nociceptive, locomotory and ingestive behaviors of an island population of wild male and female deer mice, Peromyscus maniculatus triangularis. The prototypical mu opiate agonist, morphine, had significant analgesic and locomotory effects, which were blocked by naloxone, and the specific delta opiate antagonist, ICI 154,129, respectively. The specific kappa opiate agonist, U-50,488, had significant analgesic actions and inhibitory effects on locomotor activity, as well as stimulating feeding. Significant day-night variations occurred in the analgesic and activity responses, with the mu and kappa opiate agonists having significantly greater effects at night. There were also prominent sex differences in responses; male deer mice displaying significantly greater levels of mu and kappa opiate-induced analgesia and alterations in activity than female animals. These sex differences in opiate-induced effects were most pronounced at night, female deer mice displaying reduced day-night rhythms of responsiveness. These results demonstrate the existence of significant day-night rhythms and sex differences in the mu and kappa opiate behavioral responses of a wild population of rodents.

Sex differences in magnetic field inhibition of morphine-induced responses of wild deer mice, Peromyscus maniculatus triangularis.

An exposure for 60 min to a 0.5 Hz weak rotating magnetic field (1.5-90 G) reduced the day-time locomotory and analgesic effects of morphine (10 mg/kg) in a wild population of deer mice. Peromyscus maniculatus triangularis. Females displayed significantly lower levels of morphine-induced responses and sensitivity to the inhibitory effects of the magnetic fields than did the males. These responses indicate that there are sex differences in the effects of weak magnetic fields on the opiate-mediated responses of a wild rodent, with males being more responsive to the magnetic stimuli than females.

Growth of Clethrionomys gapperi and Microtus pennsylvanicus in captivity.

Growth of Clethrionomys gapperi and Microtus pennsylvanicus from southern Manitoba was documented from birth to 30 days. Clethrionomys gapperi were smaller and grew more slowly (g/day) than M. pennsylvanicus, although both species were weaned at the same age. There were significant differences in growth rates between sexes in M. pennsylvanicus and among litter sizes in both species. Most of the variability in growth was due to differences among litters. The patterns of development was similar to those reported for other North American species of Clethrionomys and Microtus.