The Influence of Morphine on Cerebral 5-HT^sub 2A^ Availability in Dogs: a SPECT Study

The opioid and serotonergic systems are closely involved in pain processing and mood disorders. The aim of this study was to assess the influence of systemic morphine on cerebral serotonin 2A receptor (5-HT^sub 2A^) binding in dogs using SPECT with the 5-HT^sub 2A^ radioligand ^sup 123^I-5I-R91150. Methods: 5-HT^sub 2A^ binding was estimated with and without morphine pretreatment in 8 dogs. The 5-HT^sub 2A^ binding indices in the frontal, parietal, temporal, and occipital cortex and in the subcortical region were obtained by semiquantification. Results: A significantly decreased 5-HT^sub 2A^ binding index was found in the morphine group for the right (morphine, 1.41 ± 0.06; control, 1.52 ± 0.10) and left(morphine, 1.44 ± 0.08; control, 1.55 ± 0.11) frontal cortices, with P = 0.012 and P = 0.040, respectively. No significant differences were noted for the other regions. Conclusion: Morphine decreased the frontocortical 5-HT^sub 2A^ availability, confirming an interaction between the 5-HTergic and the opioid systems. Whether this interaction is caused by decreased receptor density due to direct internalization or is the result of indirect actions, such as increased endogenous serotonin release, remains to be elucidated. [PUBLICATION ABSTRACT]