Morphine distribution following infusion into lateral ventricle during hibernation and euthermia

The intracerebral pattern of diffusion of 3H-morphine was studied autoradiographically following continuous infusion (4, 9, and 18 hr; 1 microliter/hr) into the lateral ventricle during hibernation and euthermia (i.e., not hibernating) in ground squirrels (Citellus lateralis). Morphine diffusion into the parenchyma during both states was extensive, resulting in increased autoradiographic optical density of 34 structures examined. The zone of radiolabeled tissue was primarily ipsilateral, and it expanded with increasing duration of infusion. Diffusion into contralateral regions was more evident in hibernation, although the total area of radiolabeled tissue was not significantly greater than that of euthermic animals. The average optical densities of autoradiographs from hibernating brains were significantly greater than those from euthermic animals, suggesting greater accumulation of labeled material during hibernation. These data suggest that neuroactive compounds released into the ventricular space can achieve widespread distribution within the brain during hibernation (in which all physiological parameters are profoundly depressed) as well as during euthermia. Thus, the apparent lack of development of physical dependence to morphine during hibernation is not due to a restricted distribution of morphine in the hibernating brain.