Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Jul 2013
Short and long-term motor and behavioral effects of diazoxide and dimethyl sulfoxide administration in the mouse after traumatic brain injury.
Traumatic brain injury (TBI) is a worldwide phenomenon that affects all ages and socioeconomic classes and results in varying degrees of immediate and delayed motor, cognitive, and emotional deficiencies. A plethora of pharmacologic interventions that target recognized initiators and propagators of pathology are being investigated in an attempt to ameliorate secondary injury processes that follow primary injury. Diazoxide (DZ), a K(ATP) channel activator, has been shown to provide short- and long-term protective effects in a variety of in vitro and in vivo cerebral ischemia models. ⋯ In addition, animals exposed to DMSO or DZ+DMSO exhibited slower swimming speed in the Morris water maze on the final day of testing. There was no therapeutic effect, however, of the treatment or vehicle on open field behavior or learning and memory function in the Morris water maze. In summary, CCI produced significant long-term impairment of motor, memory, and behavioral performance measures, and DZ administration, under the conditions used, provided no functional benefits following injury.
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Pharmacol. Biochem. Behav. · Jul 2013
2-AG into the lateral hypothalamus increases REM sleep and cFos expression in melanin concentrating hormone neurons in rats.
Orexins/hypocretins (OX) and melanin-concentrating hormone (MCH) neurons located in the lateral hypothalamus seem to modulate different stages of the sleep-wake cycle. OX are necessary for wakefulness and MCH appears to regulate rapid eye movement sleep (REMS). Likewise, endocannabinoids, the endogenous ligands for cannabinoid receptors 1 and 2 (CB1R, CB2R), also modulate REMS in rats. ⋯ We also utilized the CB1R inverse agonist AM251 to further support the involvement of this receptor, and we performed double immunofluorescence experiments to detect c-Fos, as a marker of neural activation, in OX and in MCH neurons to determine which neurons were activated. Our results indicate that 2-AG increases REMS through CB1R activation, and increases c-Fos expression in MCH neurons. These results suggest that endocannabinoid activation of the CB1R in the lateral hypothalamus, which activates MCH neurons, is one mechanism by which REMS is triggered.