The rodent amygdala contributes to the production of cannabinoid-induced antinociception

• Published in: Neuroscience Vol. 120; no. 4; pp. 1157 - 1170
• Main Authors: Manning, B.H, Martin, W.J, Meng, I.D
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.09.2003; Elsevier
• Subjects: (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo(1,2,3-de)-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone; Amygdala - anatomy & histology; Amygdala - drug effects; Amygdala - physiology; amygdaloid complex; analgesia; Analgesics - pharmacology; Analgesics - therapeutic use; Animals; basolateral nucleus of the amygdala; Benzoxazines; Biological and medical sciences; BLA; c-fos; Cannabinoids - pharmacology; Cannabinoids - therapeutic use; CeA; Cell Count; central nucleus of the amygdala; Dose-Response Relationship, Drug; Formaldehyde; Fos; Fos-LI; Fos-like immunoreactivity; GABA Agonists - pharmacology; Immunohistochemistry; Male; Medical sciences; Microinjections; Morpholines - administration & dosage; muscimol; Muscimol - pharmacology; Naphthalenes - administration & dosage; Neuropharmacology; Oncogene Proteins v-fos - metabolism; PAG; Pain - chemically induced; Pain - drug therapy; Pain - metabolism; Pain Measurement - drug effects; periaqueductal gray matter; Pharmacology. Drug treatments; Psychodysleptics: hallucinogen; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Reaction Time; rostral ventromedial medulla; RVM; Spinal Cord - anatomy & histology; Spinal Cord - metabolism; tail flick latency; TFL; WIN55,212-2; WIN55,212-2; muscimol; Fos-LI; BLA; analgesia; PAG; RVM; c-fos; amygdaloid complex; Fos; TFL; CeA; Nociception; Amygdala; Rat; Rodentia; Central nervous system; Basal ganglion; Cannabinoid; c- fos; Analgesia; Vertebrata; Mammalia; Animal; Brain (vertebrata)
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(03)00356-7

The amygdala is a temporal lobe region that is implicated in emotional information processing. The amygdala also is associated with the processing and modulation of pain sensation. Recently, we demonstrated that in nonhuman primates, the amygdala is necessary for the full expression of cannabinoid-induced antinociception [J Neurosci 21 (2001) 8238]. The antinociceptive effect of the cannabinoid receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo(1,2,3-de)-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone (WIN55,212-2) was significantly reduced in rhesus monkeys with large bilateral lesions of the amygdaloid complex. In the present study, we investigated the contribution of the amygdala to cannabinoid-induced antinociception in the rat. Using bilateral local microinjections of the GABAA receptor agonist muscimol, we inactivated neurons originating from the central nucleus of the amygdala (CeA) or basolateral nucleus of the amygdala (BLA). In rats injected with intra-CeA saline, the cannabinoid receptor agonist WIN55,212-2 produced dose-dependent antinociception on the noxious heat-evoked tail flick assay. In rats treated with intra-CeA muscimol, however, the antinociceptive effect of WIN55,212-2 was significantly reduced. Rats treated with intra-BLA muscimol showed no deficit in WIN55,212-2-induced antinociception. The effect of CeA inactivation on WIN55,212-2-induced suppression of prolonged pain in the formalin test also was tested. In rats treated with intra-CeA saline, WIN55,212-2 reduced the incidence of formalin-induced nociceptive behaviors and also reduced formalin-evoked c-fos expression in both superficial and deep laminae of the spinal cord dorsal horn. In rats treated with intra-CeA muscimol, however, these effects of WIN55,212-2 were significantly reduced. The results constitute the first causal data demonstrating the necessity of descending pain-modulatory circuitry (of which the CeA is a component) for the full expression of cannabinoid-induced antinociception in the rat. Furthermore, the results complement previous findings suggesting an overlap in neural circuitry activated by opioids and cannabinoids.