A Strong Influence of Serotonin Axons on β-Adrenergic Receptors in Rat Brain

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Abstract
The role of serotonin axons in modulating the norepinephrine neurotransmission system in rat brain was investigated. Selective lesions of the forebrain serotonergic system were made by injecting 5,7-dihydroxytryptamine into the midbrain raphe nuclei. Four to six weeks after the lesion, the uptake of 3H-labeled serotonin in the frontal cortex and the hippocampus was reduced by more than 90 percent, while neither the uptake of 3H-labeled norepinephrine nor the content of norepinephrine was affected in either tissue. The number of beta-adrenergic receptors, as measured by radioligand binding with 3H-labeled dihydroalprenolol, was increased in the frontal cortex and hippocampus of rats with lesions. Similarly, specific lesions of central serotonin axons produced by systemically administered p-chloramphetamine resulted in an increase in the binding of 3H-labeled dihydroalprenolol to beta-adrenergic receptors and in the production of adenosine 3',5'-monophosphate in response to isoproterenol. These results indicate that serotonin axons may regulate beta-adrenergic receptor number and function in brain.