Ecological divergence in the yellow-bellied kingsnake (Lampropeltis calligaster) at two North American biodiversity hotspots.

Several biogeographic barriers in the Eastern Nearctic appear to reduce gene flow among populations of many species in predictable ways, however these patterns used to infer process of divergence may be deceiving if alternative modes of diversification are not considered. By using a multilocus statistical phylogeographic approach to examine diversity within a North American snake, Lampropeltis calligaster, we find that mode and timing of speciation near the Mississippi River embayment and peninsular Florida, two main biodiversity hotspots in eastern North America, challenge previously held notions of strict vicariance as the causal factor behind patterns of divergence seen among taxa at these locations. We found three species inhabiting distinct ecological niches with divergences dating to the mid- and early-Pleistocene with subsequently stable or increasing effective population sizes, further supporting the idea that the Pleistocene was an important driver of diversification in North America. Our results lead to a revised hypothesis that ecological divergence has occurred in this group across environments associated with the Mississippi River and at the Florida peninsula. Importantly, in their western distributions, we show that species divergence is associated with the ecological transition from distinct forested habitats to grasslands, rather than the nearby Mississippi River, a barrier often implicated for many other organisms. Additionally, we stress the importance of examining each delimited lineage with respect to conservation, since ecological niche models suggest that by the end of the century changes in climate may negatively alter habitat suitability and, barring adaptation, substantially reduce the suitable range of two of the three species we identified.

Analgesic properties of loperamide differ following systemic and local administration to rats after spinal nerve injury.

BACKGROUND: The analgesic properties and mechanisms of loperamide hydrochloride, a peripherally acting opioid receptor agonist, in neuropathic pain warrant further investigation. METHODS: We examined the effects of systemic or local administration of loperamide on heat and mechanical hyperalgesia in rats after an L5 spinal nerve ligation (SNL). RESULTS: (1) Systemic loperamide (0.3-10 mg/kg, subcutaneous in the back) dose dependently reversed heat hyperalgesia in SNL rats, but did not produce thermal analgesia. Systemic loperamide (3 mg/kg) did not induce thermal antinociception in naïve rats; (2) systemic loperamide-induced anti-heat hyperalgesia was blocked by pretreatment with intraperitoneal naloxone methiodide (5 mg/kg), but not by intraperitoneal naltrindole (5 mg/kg) or intrathecal naltrexone (20 µg/10 µL); (3) local administration of loperamide (150 µg), but not vehicle, into plantar or dorsal hind paw tissue induced thermal analgesia in SNL rats and thermal antinociception in naïve rats; (4) the analgesic effect of intraplantar loperamide (150 µg/15 µL) in SNL rats at 45 min, but not 10 min, post-injection was blocked by pretreatment with an intraplantar injection of naltrexone (75 µg/10 µL); (5) systemic (3.0 mg/kg) and local (150 µg) loperamide reduced the exaggerated duration of hind paw elevation to noxious pinprick stimuli in SNL rats. Intraplantar injection of loperamide also decreased the frequency of pinprick-evoked response in naïve rats. CONCLUSIONS: These findings suggest that both systemic and local administration of loperamide induce an opioid receptor-dependent inhibition of heat and mechanical hyperalgesia in nerve-injured rats, but that local paw administration of loperamide also induces thermal and mechanical antinociception.

Tolerance, opioid-induced allodynia and withdrawal associated allodynia in infant and young rats.

Our laboratory has previously characterized age-dependent changes in nociception upon acute morphine withdrawal. This study characterizes changes in mechanical and thermal nociception following acute, intermittent, or continuous morphine administration in infant (postnatal days 5-8) and young (postnatal days 19-21) rats. Morphine was given as a single acute administration (AM), intermittently twice a day for 3 days (IM), or continuously for 72 h via pump (CM). AM did not produce long-term changes in mechanical or thermal nociception in either infant or young rats. CM produced changes in mechanical nociception that included the development of tolerance, opioid-induced mechanical allodynia and withdrawal-associated mechanical allodynia in young rats, but only tolerance and a prolonged withdrawal-associated mechanical allodynia in infant rats. IM produced withdrawal-associated mechanical allodynia in both infant and young rats. Measuring paw withdrawal responses to thermal stimuli, infant and young rats showed tolerance without opioid-induced thermal hyperalgesia or withdrawal-associated thermal hyperalgesia following CM. In contrast to CM, withdrawal-associated thermal hyperalgesia was seen in both ages following IM. In conclusion, CM versus IM differentially modified mechanical and thermal nociception, suggesting that opioid-dependent thermal hyperalgesia and mechanical allodynia can be dissociated from each other in infant and young rats. Furthermore, tolerance, opioid-induced hypersensitivity, and withdrawal-associated hypersensitivity are age-specific and may be mediated by distinct mechanisms.