Quantification of 11 Cyohimbine binding to α 2 adrenoceptors in rat brain in vivo

We quantified the binding potentials (BP ND) of 11 Cyohimbine binding in rat brain to alpha-2 adrenoceptors to evaluate 11 Cyohimbine as an in vivo marker of noradrenergic neurotransmission and to examine its sensitivity to the level of noradrenaline. Dual 11 Cyohimbine dynamic positron emission tomography (PET) recordings were applied to five Sprague Dawley rats at baseline, followed by acute amphetamine administration (2 mg/kg) to induce elevation of the endogenous level of noradrenaline. The volume of distribution (V T) of 11 Cyohimbine was obtained using Logan plot with arterial plasma input. Because alpha-2 adrenoceptors are distributed throughout the brain, the estimation of the BP ND is complicated by the absence of an anatomic region of no displaceable binding. We used the Inhibition plot to acquire the reference volume, V ND, from which we calculated the BP ND. Acute pharmacological challenge with amphetamine induced a significant decline of 11 Cyohimbine BP ND of ∼38% in all volumes of interest. The BP ND was greatest in the thalamus and striatum, followed in descending order by, frontal cortex, pons, and cerebellum. The experimental data demonstrate that 11 Cyohimbine binding is sensitive to a challenge known to increase the extracellular level of noradrenaline, which can benefit future PET investigations of pathologic conditions related to disrupted noradrenergic neurotransmission.