Methanandamide attenuates cocaine-induced hyperthermia in rats by a cannabinoid CB1-dopamine D2 receptor mechanism

Rasmussen, Bruce A.; Kim, Esther; Unterwald, Ellen M.

doi:10.1016/j.brainres.2008.12.078

Cited by 10 publications

(8 citation statements)

References 49 publications

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“…Methanandamide did not affect hyperactivity induced by acute amphetamine exposure, a finding consistent with previous work from our laboratory showing that rats pretreated with methanandamide display normal hyperactivity following acute cocaine exposure (Rasmussen et al, 2009). The inability of methanandamide to alter amphetamine- and cocaine-induced hyperactivity is different from the effects of other cannabinoid agonists on acute hyperactivity produced by psychostimulants.…”

Section: Discussionsupporting

confidence: 92%

“…Additionally, cocaine-induced hyperlocomotion is counteracted by the synthetic cannabinoind agonist HU-210, but only at doses which suppress basal locomotor activity and stereotypy (Ferrari et al, 1999). The ineffectiveness of methanandamide in our experiments may be due to the dose used because 5 mg/kg does not affect basal locomotor activity or stereotypy (Rasmussen et al, 2009). Higher doses of methanandamide do reduce basal activity (Jarbe et al, 2003), and these doses might be capable of counteracting cocaine-induced hyperactivity in a manner similar to δ 9 -THC and WIN 55212-2.…”

Section: Discussionmentioning

confidence: 95%

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Methanandamide blocks amphetamine-induced behavioral sensitization in rats

Rasmussen

Unterwald

Kim

2010

European Journal of Pharmacology

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Methanandamide acts at targets which modulate amphetamine-induced behaviors. Therefore, we investigated methanandamide effects on the acute hyperactivity produced by a single injection of amphetamine and behavioral sensitization induced by repeated amphetamine exposure in rats. Methanandamide (5 mg/kg, i.p.) did not affect basal locomotor or stereotypical activity. Methanandamide (5 mg/kg, i.p.) pretreatment did not alter the acute increase in locomotor or stereotypical activities produced by acute amphetamine (2 mg/kg, i.p.). For chronic studies, rats injected with amphetamine (2 mg/kg, i.p.) once daily for 3 consecutive days were then challenged with amphetamine (2 mg/kg, i.p.) 5 days later. Expression of locomotor sensitization was blocked when methanandamide (5 mg/kg, i.p.) was given once, just prior to amphetamine (2 mg/kg, i.p.) challenge. In rats co-exposed to methanandamide (5 mg/kg, i.p.) and amphetamine (2 mg/kg, i.p.) on days 1-3 and then challenged with amphetamine (2 mg/kg, i.p.) following 5 days of drug absence, the development of both locomotor and stereotypical sensitization was blocked. The ability of methanandamide to block amphetamine-sensitized behaviors suggests that this pharmacologically diverse lipid regulates signaling events impacted by repeated psychostimulant exposure.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 95%

Methanandamide blocks amphetamine-induced behavioral sensitization in rats

Rasmussen

Unterwald

Kim

2010

European Journal of Pharmacology

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“…In addition to these direct cortical mechanisms, cannabinoids may impact noradrenergic transmission via actions on the coeruleo-cortical pathway through regulation of NE synthesis (Page et al, 2007; Moranta et al, 2004), alterations in CB1 receptor mRNA in LC neurons (Herkenham et al, 1990; Hohmann and Herkenham, 1999) or presynaptic influences within the LC, the source of NE afferents to the PFC. Finally, interactions may occur at the receptor level as recent data indicate that CB1 receptors form homo- and heteromeric complexes with other catecholamine receptors (Laviolette and Grace, 2006; Rasmussen et al, 2009). Physical interactions have been reported between CB1r and β2-AR and, in human embryonic kidney 293H cells, co-expression of β2-AR tempered the constitutive activity and increased cell surface expression of CB1rs (Hudson et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Stress-induced sensitization of cortical adrenergic receptors following a history of cannabinoid exposure

Reyes

Szot

Sikkema

et al. 2012

Experimental Neurology

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The cannabinoid receptor agonist, WIN 55,212-2, increases extracellular norepinephrine levels in the rat frontal cortex under basal conditions, likely via desensitization of inhibitory α2-adrenergic receptors located on norepinephrine terminals. Here, the effect of WIN 55,212-2 on stress-induced norepinephrine release was assessed in the medial prefrontal cortex (mPFC), in adult male Sprague-Dawley rats using in vivo microdialysis. Systemic administration of WIN 55,212-2 thirty minutes prior to stressor exposure prevented stress-induced cortical norepinephrine release induced by a single exposure to swim when compared to vehicle. To further probe cortical cannabinoid-adrenergic interactions, postsynaptic α2-adrenergic receptor (AR)-mediated responses were assessed in mPFC pyramidal neurons using electrophysiological analysis in an in vitro cortical slice preparation. We confirm prior studies showing that clonidine increases cortical pyramidal cell excitability and that this was unaffected by exposure to acute stress. WIN 55,212-2, via bath application, blocked postsynaptic α2-AR mediated responses in cortical neurons irrespective of exposure to stress. Interestingly, stress exposure prevented the desensitization of α2-AR mediated responses produced by a history of cannabinoid exposure. Together, these data indicate the stress-dependent nature of cannabinoid interactions via both pre- and postsynaptic ARs. In summary, microdialysis data indicate that cannabinoids restrain stress-induced cortical NE efflux. Electrophysiology data indicate that cannabinoids also restrain cortical cell excitability under basal conditions; however, stress interferes with these CB1-α2 AR interactions, potentially contributing to over-activation of pyramidal neurons in mPFC. Overall, cannabinoids are protective of the NE system and cortical excitability but stress can derail this protective effect, potentially contributing to stress-related psychopathology. These data add to the growing evidence of complex, stress-dependent modulation of monoaminergic systems by cannabinoids and support the potential use of cannabinoids in the treatment of stress-induced noradrenergic dysfunction.

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“…Furthermore, CB 1 R activation mediates central effects and more particularly the addictive properties of cannabinoids such as tetrahydrocannabinol (THC), the main psychoactive ingredient of marihuana [120]. In view of the potential role of CB 1 R-D 2 R heteromer and A 2 R antagonists as potential therapeutic agents in drug dependence [121–123], the antagonistic CB 1 R-D 2 R interactions may also involve the A 2 R [124–126]. A 2 R may play a role in the behavioral inhibition exerted by the CB 1 R agonist on D 2 R agonist-induced locomotor hyperactivity.…”

Section: Adenosine and Dopamine Receptor Heteromersmentioning

confidence: 99%

Heteromerization of G Protein-Coupled Receptors: Relevance to Neurological Disorders and Neurotherapeutics

Albizu¹,

Moreno²,

González-Maeso³

et al. 2010

CNSNDDT

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Because G protein-coupled receptors (GPCRs) are numerous, widely expressed and involved in major physiological responses, they represent a relevant therapeutic target for drug discovery, particularly regarding pharmacological treatments of neurological disorders. Among the biological phenomena regulating receptor function, GPCR heteromerization is an important emerging area of interest and investigation. There is increasing evidence showing that heteromerization contributes to the pharmacological heterogeneity of GPCRs by modulating receptor ontogeny, activation and recycling. Although in many cases the physiological relevance of receptor heteromerization has not been fully established, the unique pharmacological and functional properties of heteromers are likely to lead to new strategies in clinical medicine. This review describes the main GPCR heteromers and their implications for major neurological disorders such as Parkinson’s disease, schizophrenia and addiction. A better understanding of molecular mechanisms underlying drug interactions related to the targeting of receptor heteromers could provide more specific and efficient therapeutic agents for the treatment of brain diseases.

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Methanandamide attenuates cocaine-induced hyperthermia in rats by a cannabinoid CB1-dopamine D2 receptor mechanism

Cited by 10 publications

References 49 publications

Methanandamide blocks amphetamine-induced behavioral sensitization in rats

Methanandamide blocks amphetamine-induced behavioral sensitization in rats

Stress-induced sensitization of cortical adrenergic receptors following a history of cannabinoid exposure

Heteromerization of G Protein-Coupled Receptors: Relevance to Neurological Disorders and Neurotherapeutics

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