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The amygdala is a sensory integration center that plays an important role in emotional learning, behavior, and motivation. Cannabinoid signaling in the amygdala modulates aspects of anxiety, aggression, and fear in rodents via cannabinoid receptor 1, however little is known about cannabinoid signaling in the amygdala of humans and nonhuman primates. Primates are behaviorally diverse, with closely related species often displaying distinct social styles characterized by varying degrees of social tolerance and agonistic tendencies. Such behavioral differences are thought to be associated with neurochemical differences among species. Given what is known about the functional role of cannabinoid signaling in the amygdala, we tested whether relatively tolerant species, such as humans, bonobos, and marmosets, possess relatively higher cannabinoid receptor 1-immunoreactive (CB1R-ir) axon density in the basolateral amygdala. We used immunohistochemistry and stereological methods to compare CB1R-ir axon density among 47 primates representing nine species: humans (n=5), chimpanzees (n=6), bonobos (n=2), baboons (n=6), rhesus macaques (n=5), Japanese macaques (n=6), pigtail macaques (n=6), marmosets (n=5), and capuchins (n=6). The basolateral amygdala is comprised of the lateral, basal, and accessory basal nuclei. Stereological data for each nucleus was collected separately. After ruling out sex differences within each species, we used repeated measures ANOVA to evaluate species differences. The interaction (F16,76 = 5.061, p<.001) and main effects of species (F8,38 = 8.007, p<.001) and area (F2,76 = 59.616, p<.001) were all significant. However, the observedspecies differences did not support our hypothesis related to social tolerance nor did the data conform to a phylogenetic pattern. Instead, we found that while some closely related species differed from each other in a nucleus-dependent manner, some distantly related species shared unexpected similarities. Our results highlight the need for additional comparative work on the cannabinoid system from a molecular and genetic perspective. We discuss the implications of our observations with special focus on primate brain evolution and its connection to primate social style. 

Previously identified differences in serotonin innervation have been proposed to underlie differences in behavior, such as personality style and sociability. Contrasting serotonergic fiber densities have been found in the amygdala of chimpanzees versus bonobos, and humans and apes are known to have more serotonin than monkeys in the dorsal and medial caudate nucleus and dorsal putamen. Our present work builds on earlier results by examining serotonergic axon innervation density in the nucleus accumbens and ventral pallidum, two important nodes in the reward system. The present sample included humans (n = 6; NIH NeuroBioBank), pigtailed macaque monkeys (n = 5; National Primate Research Center, University of Washington), and capuchin monkeys (n = 6; Alpha Genesis). All individuals were adult and free of neuropathological alterations. Brain sections were immunohistochemically processed for serotonin transporter (SERT) (Millipore, MAB 5618), and stereological methods (SpaceBalls probe, MBF Bioscience) were used to quantify the length density of SERT-immunoreactive axons and neuron densities from adjacent Nissl-stained sections. Repeated measures ANOVA was used to evaluate differences of SERT-immunoreactive axon densities and neuron densities among species. The main effect of brain region was significant (F 1,2 = 12.25, p = 0.004) with greater SERT innervation in ventral pallidum compared to the nucleus accumbens in all species. The main effect of species and the interaction of species x brain region were not significant. Based on these results, the serotonergic system in the nucleus accumbens and ventral pallidum appears to be evolutionarily conserved in the amount of innervation supplied to neurons among human and other anthropoid primates.