Reduction in opioid- and cannabinoid-induced antinociception in rhesus monkeys after bilateral lesions of the amygdaloid complex.
The amygdaloid complex is a prominent temporal lobe region that is associated with "emotional" information processing. Studies in the rodent have also recently implicated the amygdala in the processing and modulation of pain sensation, the experience of which involves a considerable emotional component in humans. In the present study, we sought to establish the relevance of the amygdala to pain modulation in humans by investigating the contribution of this region to antinociceptive processes in nonhuman primates. Using magnetic resonance imaging guidance, the amygdaloid complex was lesioned bilaterally in six rhesus monkeys (Macaca mulatta) through microinjection of the neurotoxin ibotenic acid. This procedure resulted in substantial neuronal cell loss in all nuclear subdivisions of this structure. In awake unoperated control monkeys, systemic administration of the prototypical opioid morphine or the cannabinoid receptor agonist WIN55,212-2 produced dose-dependent antinociception on a warm-water tail-withdrawal assay. The antinociceptive effects of each drug were reversible with an appropriate antagonist. In monkeys with bilateral amygdala lesions, however, the antinociceptive effects of each drug were significantly reduced. These results constitute the first causal data demonstrating the necessity of neurons in a specific brain region for the full expression of opioid- and cannabinoid-induced antinociception in the primate. Because our amygdala-lesioned monkeys exhibited both a reduction in antinociception and a reduction in behavioral indices of fear (Emery et al., 2001), the possibility should be considered that, in the primate, "antinociceptive circuitry" and "fear circuitry" overlap at the level of the amygdala.
Manning
B H
BH
Department of Neuroscience, Merck Research Laboratories, Merck & Company, West Point, Pennsylvania 19486-0004, USA. barton_manning@merck.com
Merin
N M
NM
Meng
I D
ID
Amaral
D G
DG
D000679:Amygdala / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D048588:Benzoxazines; D002186:Cannabinoids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects / Q000502:physiology; D007051:Ibotenic Acid / Q000008:administration & dosage; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D014851:Wakefulness
D000700:Analgesics; D048588:Benzoxazines; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D009294:Narcotics; D007051:Ibotenic Acid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D009020:Morphine