Effect of Δ9-tetrahydrocannabinol on hypothalamic thermosensitive units

Schmeling, William T.; Hosko, Michael J.

doi:10.1016/0006-8993(80)90213-9

Cited by 15 publications

(6 citation statements)

References 33 publications

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“…This differential effectiveness of rimonabant can be attributed to these end points being mediated by supraspinal versus spinal and peripheral loci of action. Cannabinoid-induced hypothermia is predominantly mediated by the preoptic area of the hypothalamus (Fitton and Pertwee 1982; Schmeling and Hosko 1980), which is adjacent to the third ventricle and is consistent with our observations shown in Fig. 2b.…”

Section: Discussionsupporting

confidence: 92%

CB1 receptors mediate rimonabant-induced pruritic responses in mice: investigation of locus of action

et al. 2011

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Rationale Cannabinoids have recently been identified as potential neuronal modulators of pruritic response, representing a potential target in the treatment of itch associated with a variety of pathophysiologic conditions. While the selective CB1 receptor antagonist rimonabant is an established pruritic agent in both animal and clinical testing, its receptor mechanism of action and anatomical loci remain unclear. Objective The purpose of this study was to determine whether CB1 receptor blockade is critical to rimonabant-induced scratching and to identify differences in scratching response based on different routes of administration. Furthermore, experiments were designed to elucidate any evidence as to whether rimonabant elicits scratching behavior through common immunologic hypersensitivity mechanisms. Results Rimonabant was equally effective at producing scratching via intraperitoneal and local subcutaneous injection. This compound also produced an intense scratching response when administered intrathecally, but had no effects after intracerebroventricular administration. Repeated administration of rimonabant led to a decreased magnitude of scratching. While rimonabant-induced scratching was not attenuated either by pretreatment with the H1 receptor antagonist loratadine or in mast cell-deficient mice, it lacked efficacy in CB1 (−/−) mice. Conclusions Rimonabant is a potent and fully effective pruritogen when administered spinally or systemically and requires CB1 receptors to induce scratching, suggesting an important spinal CB1 receptor component of action. The lack of responsiveness to H1 antagonism or mast cell deficiency supports previous findings that cannabinoids modulate itch through neuronal mechanisms, and not by traditional hypersensitivity activation.

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Section: Discussionsupporting

confidence: 92%

CB1 receptors mediate rimonabant-induced pruritic responses in mice: investigation of locus of action

et al. 2011

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“…al., 2000). Conversely, cannabinoid CB 1 receptor activation directly decreases thermogenesis (Perwitz et al, 2006), and also decreases the firing rate and increases the thermosensitivity of the primary preoptic thermodetector units (Schmeling and Hosko, 1980). Warm-sensitive neurons express an I A like the one enhanced by cannabinoid CB 1 receptor agonists in this and other studies (Deadwyler et.…”

Section: Discussionmentioning

confidence: 99%

Estrogen rapidly attenuates cannabinoid-induced changes in energy homeostasis

Kellert

Nguyen

et al. 2009

European Journal of Pharmacology

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We examined whether estrogen negatively modulates cannabinoid-induced regulation of food intake, core body temperature and neurotransmission at proopiomelanocortin (POMC) synapses. Food intake was evaluated in ovariectomized female guinea pigs abdominally implanted with thermal DataLoggers and treated s.c. with the cannabinoid CB 1 /CB 2 receptor agonist WIN 55,212-2, the CB 1 receptor antagonist AM251 or their cremephor/ethanol/0.9% saline vehicle, and with estradiol benzoate (EB) or its sesame oil vehicle. Whole-cell patch clamp recordings were performed in slices through the arcuate nucleus. WIN 55,212-2 produced dose-and time-dependent increases in food intake. EB decreased food intake 8-24 h after administration, but rapidly and completely blocked the increase in consumption caused by WIN 55,212-2. EB also attenuated the WIN 55,212-2-induced decrease in core body temperature. The AM251-induced decrease in food intake was unaffected. The diminution of the WIN 55,212-2-induced increase in food intake caused by EB correlated with a marked attenuation of cannabinoid receptor-mediated decreases in glutamatergic miniature excitatory postsynaptic current frequency occurring within 10-15 minutes of steroid application. Furthermore, EB completely blocked the depolarizing shift in the inactivation curve for the A-type K + current caused by WIN 55,212-2. The EB-mediated, physiologic antagonism of these presynaptic and postsynaptic actions elicited upon cannabinoid receptor activation was observed in arcuate neurons immunopositive for phenotypic markers of POMC neurons. These data reveal that estrogens negatively modulate cannabinoid-induced changes in appetite, body temperature and POMC neuronal activity. They also impart insight into the neuroanatomical substrates and effector systems upon which these counter-regulatory factors converge in the control of energy homeostasis.

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“…In addition to the neurochemical analyses, cannabinoid‐induced hypothermia (Schmeling and Hosko, 1980) was also quantified before (15 min) and after (45 min) the various drug treatments. Specifically, the hypothermic response induced by WIN55212‐2 was assessed to monitor a well‐known pharmacologic effect to this agonist in parallel with the neurochemical analyses (acute vs. chronic treatment).…”

Section: Methodsmentioning

confidence: 99%

Acute, chronic and withdrawal effects of the cannabinoid receptor agonist WIN55212‐2 on the sequential activation of MAPK/Raf‐MEK‐ERK signaling in the rat cerebral frontal cortex: Short‐term regulation by intrinsic and extrinsic pathways

Moranta

Esteban

Garcı́a-Sevilla

2006

J of Neuroscience Research

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The cannabinoids (CB) modulate the extracellular signal-regulated kinase (ERK), leading to various forms of plasticity in the brain. Little is known, however, on the in vivo short- and long-term activation and regulation of the components of mitogen-activated protein kinase (MAPK)/ERK signaling by CB. The CB agonist WIN55212-2 (8 mg/kg) increased the immunodensities of phosphorylated c-Raf-1 (42%), MEK1/2 (63%), ERK1 (24%), and ERK2 (28%) in the rat cerebral frontal cortex. These effects were antagonized by SR141716A (rimonabant, 10 mg/kg), a selective CB(1) receptor antagonist. Repeated WIN55212-2 treatment (2-8 mg/kg for 5 days) resulted in tachyphylaxis to the acute activation of Raf-MEK-ERK signaling. Acute WIN55212-2 also induced a hypothermic effect in rats, which was reduced after repeated administration (tolerance). Treatment with SR141716A after chronic WIN55212-2 resulted in the expected cannabinoid withdrawal syndrome, without concomitant alterations in the phosphorylation state of c-Raf-1, MEK1/2, or ERK1/2. Pretreatment with SL327 (20 mg/kg, a MEK1/2 inhibitor) increased the basal phosphorylation of c-Raf-1 (40%) and MEK1/2 (74%; feedback regulation) and fully prevented the up-regulation of ERK1/2 (23-31%) induced by WIN55212-2. Pretreatment with MK801 (1 mg/kg, a NMDA receptor antagonist) effectively blocked the up-regulation c-Raf-1 (41%), MEK1/2 (57%) and ERK1/2 (25-30%) induced by the CB agonist. The main findings demonstrate that the acute stimulation of CB(1) receptors in the frontal cortex results in the sequential phosphorylation of Raf-MEK-ERK cascade, in which c-Raf-1 activation (rate-limiting process) plays a crucial role. Moreover, the in vivo stimulating effect of WIN55212-2 on Raf-MEK-ERK signaling is under the extrinsic regulation of an excitatory glutamatergic mechanism.

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Effect of Δ9-tetrahydrocannabinol on hypothalamic thermosensitive units

Cited by 15 publications

References 33 publications

CB1 receptors mediate rimonabant-induced pruritic responses in mice: investigation of locus of action

CB1 receptors mediate rimonabant-induced pruritic responses in mice: investigation of locus of action

Estrogen rapidly attenuates cannabinoid-induced changes in energy homeostasis

Acute, chronic and withdrawal effects of the cannabinoid receptor agonist WIN55212‐2 on the sequential activation of MAPK/Raf‐MEK‐ERK signaling in the rat cerebral frontal cortex: Short‐term regulation by intrinsic and extrinsic pathways

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