PET Imaging of Serotoninergic Neurotransmission with [¹¹C]DASB and [¹⁸F]altanserin after Focal Cerebral Ischemia in Rats

Abstract

The use of selective serotonin reuptake inhibitors has shown functional improvement after stroke. Despite this, the role of serotoninergic neurotransmission after cerebral ischemia evolution and its involvement in functional recovery processes are still largely unknown. For this purpose, we performed in parallel in vivo magnetic resonance imaging and positron emission tomography (PET) with [ 11 C]DASB and [ 18 F]altanserin at 1, 3, 7, 14, 21, and 28 days after middle cerebral artery occlusion (MCAO) in rats. In the ischemic territory, PET with [ 11 C]DASB and [ 18 F]altanserin showed a dramatic decline in serotonin transporter (SERT) and 5-HT 2A binding potential in the cortex and striatum after cerebral ischemia. Interestingly, a slight increase in [ 11 C]DASB binding was observed from days 7 to 21 followed by the uppermost binding at day 28 in the ipsilateral midbrain. In contrast, no changes were observed in the contralateral hemisphere by using both radiotracers. Likewise, both functional and behavior testing showed major impaired outcome at day 1 after ischemia onset followed by a recovery of the sensorimotor function and dexterity from day 21 to day 28 after cerebral ischemia. Taken together, these results might evidence that SERT changes in the midbrain could have a key role in the functional recovery process after cerebral ischemia.

Rewiring of the Serotonin System in Major Depression

“…In living patients, this has been evaluated in positron emission tomography studies using ligands such as 11 C-DASB. This is supported by the loss of DASB binding in cortex and striatum following MCAO in rats, with a gradual recovery over 3 weeks ( 128 ), similar to the time course that we observed in post-ischemic mice ( 64 ). Using 11 C-DASB to label 5-HTT, a reduced 5-HTT ratio between dorsal raphe/ventral striatum was seen in unmedicated depressed compared to healthy controls, suggesting reduced 5-HT innervation to this reward processing center ( 261 ).…”

“…Using techniques such as receptor autoradiography, immunohistochemistry, and EM imaging has shown for monoamines a mismatch between the location of NTs relative to synaptic structures ( 103 , 126 , 127 ). For example, Martin et al ( 128 ) showed that 94% of tyrosine hydroxylase-positive boutons in macaque prefrontal cortex Area 10 had no identifiable synaptic association in non-human primates ( 129 ). Rice et al ( 130 ) modeled dopamine release to show that the presence of dopamine outside of the synaptic zone in the nigrostriatal pathway could be due to the spillover from the synaptic cleft and release into the surrounding extracellular space.…”

The Effects of Naturalistic Light on Diurnal Plasma Melatonin and Serum Cortisol Levels in Stroke Patients during Admission for Rehabilitation: A Randomized Controlled Trial

“…Since melatonin is synthetized from serotonin, it is reasonable to believe that melatonin production could be affected by the known reduction/ disturbances of serotonin synthesis after stroke 26,27. This could explain the absence of a melatonin secretion peak in our study.…”

Opposite alterations of 5­HT2A receptor brain density in subjects with schizophrenia: relevance of radiotracers pharmacological profile

“…[ 18 F]altanserin was produced in a TRACERlab FXFN synthesis module (GE Healthcare) by radiofluorination of nitro-altanserin (ABX, Radeberg, Germany) as previously published 31 . Specific activity at initial incubation time (see below) was in the range 300–700 GBq/μmol.…”