Involvement of the Cannabinoid CB₁ Receptor in the Opioid Inhibition of the Response to Cholecystokinin and Acute Withdrawal Response

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• 作者：Luca Romanelli ; Maura Palmery ; Paolo Tucci ; Maria Carmela Amico ; Luigi Antonio Morrone and Pacifico Valeri
• 关键词：Opioid ; Cannabinoid ; Acute withdrawal ; SR141716 ; WIN 55 ; 212-2
• 刊名：Neurotoxicology
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：26
• 期：5
• 页码：819-827
• 全文大小：279 K

文摘

Numerous recent studies have reported major functional interactions between cannabinoid and opioid systems. These interactions can be studied in the myenteric plexus-longitudinal muscle isolated preparations. We had previously shown that in the guinea-pig ileum (GPI), the opioid acute withdrawal response is under the inhibitory control of several systems; μ-opioid agonist exposure indirectly activates the κ-opioid system; conversely, exposure to a κ-opioid agonist indirectly activates the μ-system; the indirectly activated opioid system inhibits the withdrawal response. The adenosine A₁ system is also indirectly activated by opioids and it inhibits the withdrawal response. We had also shown that indirect activation is prevented or antagonized by cholecystokinin (CCK-8).

In GPI preparations briefly exposed to the μ-agonist, dermorphine (DERM) and then challenged with naloxone (NL), the cannabinoid CB₁ antagonist, SR141716 (SR), increased the withdrawal responses to NL, but only did so in presence of a κ-opioid and an adenosine A₁ antagonist. Under similar experimental conditions, SR also enhances the κ-opioid withdrawal response. In opioid agonist/CCK-8/NL tests, SR antagonized the inhibition of the tissue response to CCK-8 induced by the μ- or κ-opioid agonist and increased the κ-withdrawal response, but not the μ-withdrawal response. However, the dose–response curve against dermorphine inhibition of the response to CCK-8 was bell-shaped and the highest SR concentration also significantly decreased the μ-withdrawal response. In preparations exposed to dermorphine or to the κ-agonist, U-50,488H, the cannabinoid agonist WIN 55,212-2 increased the opioid-induced inhibition of the tissue response to CCK-8 and decreased the NL-induced responses.

These results show that opioid exposure may also activate the cannabinoid CB₁ system, which leads to an inhibition of the opioid acute withdrawal response. This phenomenon and the antagonistic effect of SR on the opioid-induced inhibition of the response to CCK-8 suggest that reciprocal interaction between opioid and cannabinoid systems are operating in the enteric nervous system.