ABSTRACT
Behaviors associated with sickness (food consumption, weight maintenance, exploratory activity and grooming frequency) were examined on post-surgical days 1, 3, 5, 7 and 9 in male rats treated with progesterone (4 mg/kg) and/or vehicle. Rats with medial frontal cortex contusions showed reduced food consumption on days 1 and 3 (p < 0.01), reduced weight maintenance on days 1, 3, 5, 7 and 9 (p < 0.01), reduced grooming frequency on day 1 (p < .01), and reduced exploratory activity on day 1 (p < 0.01), after injury compared to sham rats. Contusion induced behaviors were not attenuated with 5 days of progesterone treatment (p > 0.05). Progesterone did reduce lesion size at 9 days after injury (p < 0.05). Our results suggest sickness behaviors occur after traumatic brain injury and that they might not respond to some neurosteroidal agents.
Subject(s)
Brain Injuries/drug therapy , Brain Injuries/psychology , Frontal Lobe/injuries , Illness Behavior/drug effects , Progesterone/therapeutic use , Animals , Body Weight/drug effects , Disease Models, Animal , Drug Evaluation, Preclinical/methods , Eating/drug effects , Exploratory Behavior/drug effects , Frontal Lobe/drug effects , Frontal Lobe/pathology , Grooming/drug effects , Male , Progesterone/pharmacology , Rats , Rats, Sprague-DawleyABSTRACT
Odor mixtures can produce several qualitatively different percepts; it is not known at which stage of processing these are determined. We asked if activity within the first stage of olfactory processing, the glomerular layer of the olfactory bulb, predicts odor mixture perception. We characterized how mice respond to components after training to five different mixture ratios of pentanal and hexanal, and found two types of responses: elemental perception and overshadowing. We then used intrinsic signal imaging to observe glomerular activity in response to the same mixtures and their components. As has been previously described, glomerular activity patterns produced by mixtures resemble the linear combination of responses to components. Mice trained to identify mixtures with more hexanal than pentanal recognized hexanal but not pentanal when the odorants were presented alone (overshadowing). Consistent with these behavioral responses, the imaged activity pattern in response to mixtures was similar to that produced to hexanal alone. Moreover, there was no significant effect of glomerular inhibition in the imaged response. In contrast, the glomerular activity patterns did not predict elemental perception: when trained to identify mixtures with more pentanal than hexanal, mice recognized both components equally well, even with highly overlapping activation patterns. This suggests that spatial activity patterns within the olfactory bulb are not always sufficient to specify component recognition in mixtures.
Subject(s)
Neurons, Afferent/physiology , Odorants , Olfactory Bulb/physiology , Olfactory Pathways/physiology , Smell/physiology , Action Potentials/drug effects , Action Potentials/physiology , Aldehydes/pharmacology , Animals , Male , Mice , Mice, Inbred C57BL , Neurons, Afferent/drug effects , Neuropil/drug effects , Neuropil/physiology , Olfactory Bulb/drug effects , Olfactory Pathways/drug effects , Perception/drug effects , Perception/physiology , Sensory Thresholds/drug effects , Sensory Thresholds/physiology , Smell/drug effects , Synaptic Transmission/drug effects , Synaptic Transmission/physiologyABSTRACT
The effects of progesterone on the cellular inflammatory response to frontal cortex injury were examined on postsurgical days 1, 3, 5, 7 and 9 in male rats treated with progesterone (4 mg/kg) and/or vehicle. Rats with bilateral contusions showed increased levels of edema on days 1, 3 and 5, more reactive astrocytes on days 3, 5, 7 and 9, and more macrophages/activated microglia on days 1, 3, 5 and 9 compared to shams. The number of neurons in the medial dorsal nucleus (MDN) of the thalamus reduced on days 5 and 9 after injury compared to shams. Progesterone reduced edema levels and increased the accumulation of macrophages/activated microglia compared to vehicle controls (p<0.025); however, these changes in the inflammatory response were not related to MDN neuronal survival. Our results confirm the possibility that one way progesterone mediates its neuroprotective effects following injury is through its actions on the inflammatory response.