Antinociceptive, behavioural and neuroendocrine effects of CP 55,940 in young rats

Romero, Eva; Martín-Fernández, Beatriz; Sagredo, Onintza; Gómez, Núria; Urigüen, Leyre; Guaza, Carmen; Miguel, Rosario de; Ramos, J.A.; Viveros, María-Paz

doi:10.1016/s0165-3806(02)00306-1

Cited by 79 publications

(66 citation statements)

References 33 publications

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“…These differences occurred across all stages of the estrous cycle of the females, suggesting that hormonal levels were not the primary mediators of these differences (Tseng and Craft, 2001;Tseng et al, 2004). Furthermore, prepubertal female rats also showed greater sensitivity to the antinociceptive effects of the synthetic cannabinoid CP 55,940 compared with their male counterparts (Romero et al, 2002); however, similar to the results of the present study, adolescents of both sexes showed comparable locomotor effects (Romero et al, 2002). (Age differences were not directly evaluated in either of these previous studies.)…”

Section: Discussionmentioning

confidence: 98%

Pharmacological Effects of Acute and Repeated Administration of Δ⁹-Tetrahydrocannabinol in Adolescent and Adult Rats

Wiley

O'Connell²,

Tokarz³

et al. 2006

J Pharmacol Exp Ther

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Adolescents of many mammalian species exhibit rapid physiological change that is accompanied by behaviors such as increased risk taking and social interaction with peers. Marijuana abusers frequently report that their initial use occurred during adolescence. Our goal was to determine whether the in vivo effects of ⌬ 9 -tetrahydrocannabinol (⌬ 9 -THC) differed in adolescent and adult rats. Following initial testing with ⌬ 9 -THC in adolescent [postnatal day (PN)29] and adult (ϾPN60) rats of both sexes, we injected rats twice daily with 10 mg/kg ⌬ 9 -THC or vehicle for 9.5 days. Subsequently, rats were again injected with their initial dose of ⌬ 9 -THC and tested. In all rats, ⌬ 9 -THC produced dose-dependent locomotor suppression, antinociception, hypothermia and catalepsy. Some age-dependent differences in potency and efficacy were noted. Although ⌬ 9 -THC dose-effect functions were more similar across age after repeated exposure, subchronic dosing produced greater change in the hypothermic and locomotor effects of ⌬ 9 -THC in adolescents, but less change in its antinociceptive effects. These results suggest that the effects of initial exposure to ⌬ 9 -THC may not be entirely predictive of the effects of repeated exposure. Despite similarities in pharmacological effects of ⌬ 9 -THC after repeated use, adolescents and adults may exhibit differences in the pattern of transition from use to abuse.

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Section: Discussionmentioning

confidence: 98%

Pharmacological Effects of Acute and Repeated Administration of Δ⁹-Tetrahydrocannabinol in Adolescent and Adult Rats

Wiley

O'Connell²,

Tokarz³

et al. 2006

J Pharmacol Exp Ther

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“…Thus, CP55,940, used in combination with CB 1 knockout (KO) and CB 2 KO mice, represents a useful pharmacological tool for studying the functions of CB 1 and CB 2 receptors in vivo. CP55,940 has been reported to possess antinociceptive efficacy in various preclinical pain models, including acute pain, inflammatory pain, and neuropathic pain induced by traumatic nerve injury (Lichtman and Martin, 1997;Hohmann et al, 1999;Romero et al, 2002;Scott et al, 2004;Choong et al, 2007;Sain et al, 2009). Pharmacological antagonism of CB 1 receptors alone (Lichtman and Martin, 1997;Romero et al, 2002;Choong et al, 2007) or of both CB 1 and CB 2 receptors (Scott et al, 2004) blocks the antinociceptive effects of CP55,940 in rats; however, a study using CB 1 KO and CB 2 KO mice reported that the antinociceptive effects of systemic CP55,940 (at 0.3 mg/kg, i.p.…”

Section: Introductionmentioning

confidence: 99%

CB₁ Knockout Mice Unveil Sustained CB₂-Mediated Antiallodynic Effects of the Mixed CB₁/CB₂ Agonist CP55,940 in a Mouse Model of Paclitaxel-Induced Neuropathic Pain

et al. 2015

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Cannabinoids suppress neuropathic pain through activation of cannabinoid CB 1 and/or CB 2 receptors; however, unwanted CB 1 -mediated cannabimimetic effects limit clinical use. We asked whether CP55,940 [(2)-3-[2-hydroxy-4-(1,1-dimethylheptyl) phenyl]-4-(3-hydroxypropyl)cyclohexanol], a potent cannabinoid that binds with similar affinity to CB 1 and CB 2 in vitro, produces functionally separable CB 1 -and CB 2 -mediated pharmacological effects in vivo. We evaluated antiallodynic effects, possible tolerance, and cannabimimetic effects (e.g., hypothermia, catalepsy, CB 1 -dependent withdrawal signs) after systemic CP55,940 treatment in a mouse model of toxic neuropathy produced by a chemotherapeutic agent, paclitaxel. The contribution of CB 1 and CB 2 receptors to in vivo actions of CP55,940 was evaluated using CB 1 knockout (KO), CB 2 KO, and wild-type (WT) mice. Low-dose CP55,940 (0.3 mg/kg daily, i.p. ) suppressed paclitaxel-induced allodynia in WT and CB 2 KO mice, but not CB 1 KO mice. Low-dose CP55,940 also produced hypothermia and rimonabantprecipitated withdrawal in WT, but not CB 1 KO, mice. In WT mice, tolerance developed to CB 1 -mediated hypothermic effects of CP55,940 earlier than to antiallodynic effects. High-dose CP55,940 (10 mg/kg daily, i.p.) produced catalepsy in WT mice, which precluded determination of antiallodynic efficacy but produced sustained CB 2 -mediated suppression of paclitaxelinduced allodynia in CB 1 KO mice; these antiallodynic effects were blocked by the CB 2 antagonist 6-iodopravadoline (AM630). Highdose CP55,940 did not produce hypothermia or rimonabantprecipitated withdrawal in CB 1 KO mice. Our results using the mixed CB 1 /CB 2 agonist CP55,940 document that CB 1 and CB 2 receptor activations produce mechanistically distinct suppression of neuropathic pain. Our study highlights the therapeutic potential of targeting cannabinoid CB 2 receptors to bypass unwanted central effects associated with CB 1 receptor activation.

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“…Indeed, low doses of CP55,940 (Genn et al, 2003;Marco et al, 2004), nabilone (Onaivi et al, 1990), and THC (Berrendero and Maldonado, 2002) exerted anxiolytic-like effects in the light-dark crossing test and in the elevated plus-maze in adult rodents. Low-dose CP55,940 was also anxiolytic in other models of anxiety in adult, juvenile, or infant rodents (Romero et al, 2002a;Borcel et al, 2004;Genn et al, 2004). In contrast, at medium to high doses, CP55,940 or HU-210 displayed anxiogenic effects in the same or other experimental paradigms in adult as well as in juvenile or infant animals (McGregor et al, 1996a,b;Rodriguez de Fonseca et al, 1996;Giuliani et al, 2000;Arevalo et al, 2001;Marin et al, 2002;Romero et al, 2002;Genn et al, 2003;Marin Marco et al, 2004).…”

mentioning

confidence: 98%

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

2006

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Antinociceptive, behavioural and neuroendocrine effects of CP 55,940 in young rats

Cited by 79 publications

References 33 publications

Pharmacological Effects of Acute and Repeated Administration of Δ⁹-Tetrahydrocannabinol in Adolescent and Adult Rats

Pharmacological Effects of Acute and Repeated Administration of Δ⁹-Tetrahydrocannabinol in Adolescent and Adult Rats

CB₁ Knockout Mice Unveil Sustained CB₂-Mediated Antiallodynic Effects of the Mixed CB₁/CB₂ Agonist CP55,940 in a Mouse Model of Paclitaxel-Induced Neuropathic Pain

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

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Antinociceptive, behavioural and neuroendocrine effects of CP 55,940 in young rats

Cited by 79 publications

References 33 publications

Pharmacological Effects of Acute and Repeated Administration of Δ9-Tetrahydrocannabinol in Adolescent and Adult Rats

Pharmacological Effects of Acute and Repeated Administration of Δ9-Tetrahydrocannabinol in Adolescent and Adult Rats

CB1 Knockout Mice Unveil Sustained CB2-Mediated Antiallodynic Effects of the Mixed CB1/CB2 Agonist CP55,940 in a Mouse Model of Paclitaxel-Induced Neuropathic Pain

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

Contact Info

Product

Resources

About

Pharmacological Effects of Acute and Repeated Administration of Δ⁹-Tetrahydrocannabinol in Adolescent and Adult Rats

Pharmacological Effects of Acute and Repeated Administration of Δ⁹-Tetrahydrocannabinol in Adolescent and Adult Rats

CB₁ Knockout Mice Unveil Sustained CB₂-Mediated Antiallodynic Effects of the Mixed CB₁/CB₂ Agonist CP55,940 in a Mouse Model of Paclitaxel-Induced Neuropathic Pain