Neurotransmitter receptor availability in the rat brain is constant in a 24 hour-period.

Wakefulness and sleep are fundamental characteristics of the brain. We, therefore, hypothesized that transmitter systems contribute to their regulation and will exhibit circadian alterations. We assessed the concentration of various neurotransmitter receptors and transporters including adenosinergic (A1AR, A2AAR, and ENT1), dopaminergic (D1R, D2R, and DAT), and serotonergic (5-HT2AR) target proteins. Adult male Sprague Dawley rats were used and maintained in a 12 h light: 12 h dark cycle (lights on from 07:00 h to 19:00 h). We measured receptor and transporter concentrations in different brain regions, including caudate putamen, basal forebrain, and cortex in 4 hour-intervals over a 24 hour-period using quantitative in vitro autoradiography. Investigated receptors and transporters showed no fluctuations in any of the analyzed regions using one-way ANOVA. Only in the horizontal diagonal band of Broca, the difference of A1AR concentration between light and dark phases (t-test) as well as the cosinor analysis of the 24 hour-course were significant, suggesting that this region underlies receptor fluctuations. Our findings suggest that the availability of the investigated neurotransmitter receptors and transporters does not undergo changes in a 24 hour-period. While there are reports on changes in adenosine and dopamine receptors during sleep deprivation, we found no changes in the investigated adenosine, dopamine, and serotonin receptors during regular and undisturbed day-night cycles.

Acute S-ketamine application does not alter cerebral [18F]altanserin binding: a pilot PET study in humans.

Modeling short-term psychotic states with subanaesthetic doses of ketamine provides substantial experimental evidence in support of the glutamate hypothesis of schizophrenia. Ketamine exerts its pharmacological effects both directly via interactions with glutamate receptors and indirectly by stimulating presynaptic release of endogenous serotonin (5-HT). The aim of this feasibility study was to examine whether acute ketamine-induced 5-HT release interferes with the binding of the 5-HT(2A) receptor (5-HT(2A)R) radioligand [(18)F]altanserin and positron emission tomography (PET). Two subjects treated with ketamine and one subject treated with placebo underwent [(18)F]altanserin PET at distribution equilibrium conditions. Robust physiological, psychopathological and cognitive effects were present at ketamine plasma concentrations exceeding 100 microg/l during >70 min. Notwithstanding, we observed stable radioligand binding (changes +/-95% CI of -1.0 +/- 1.6% and +4.1 +/- 1.8% versus -1.2 +/- 2.6%) in large cortical regions presenting high basal uptake of both, [(18)F]altanserin and ketamine. Marginal decreases of 4% of radioligand binding were observed in the frontal lobe, and 8% in a posteriorily specified frontomesial subregion. This finding is not compatible with a specific radioligand displacement from 5-HT(2A)R which should occur proportionally throughout the whole brain. Instead, the spatial pattern of these minor reductions was congruent with ketamine-induced increases in cerebral blood flow observed in a previous study using [(15)O]butanol PET. This may caused by accelerated clearance of unspecifically bound [(18)F]altanserin from cerebral tissue with increased perfusion. In conclusion, this study suggests that [(18)F]altanserin PET is not sensitive to acute neurotransmitter fluctuations under ketamine. Advantageously, the stability of [(18)F]altanserin PET towards acute influences is a prerequisite for its future use to detect sub-acute and chronic effects of ketamine.