CROSS-SPECIES EVIDENCE FOR PSILOCIN-INDUCED VISUAL HALLUCINATIONS: RATS PERCEIVE QUALITATIVELY SIMILAR CHANGES AS HUMANS

GABAB receptors are the metabotropic GABA neurotransmitter receptors in the central nervous system constituting a fundamental part of the inhibitory modulation mechanism.These receptors are heterodimers composed of GABAB1 and GABAB2 which function is modulated by the potassium channel tetramerization domain proteins (KCTD) from clade F (KCTD16; KCTD12 and KCTD8).In our experiments we explored the possible role of the KCTD16 in modulation of nociceptive synaptic transmission in different pain models using KCTD16 KO and WT mice (obtained from B. Bettler, Uni Basel) and the transgenic mutant mice (VGAT-ChR2-EYFP crossed with KCTD16 KO).Behavioral experiments were performed to access mechanical and thermal sensitivity, whole-cell patch clamp recordings from spinal cord dorsal horn neurons was used to record miniature postsynaptic excitatory currents mEPSC, light-evoked inhibitory currents leIPSC and calcium imaging from dorsal root ganglion (DRG) neuronal cultures were also performed.Our preliminary data suggest that under control conditions the mechanical and thermal sensitivity and the excitatory and inhibitory currents recorded from the dorsal horn neurons do not differ significantly between the KO and WT mice.However, the treatment of the control animals with the GABABR agonist (baclofen) revealed a stronger effect on WT animals in comparison to the KO, producing higher thresholds for thermal and mechanical stimulation.In a model of peripheral inflammation, the KCTD16 KO mice showed a tendency to higher thermal and mechanical thresholds and there was significantly reduced inhibitory effect of Baclofen on the mEPSC and leIPSC.Our data suggest that the KCTD16 protein modulation of nociceptive synaptic transmission could play a role especially during pathological conditions, when GABABR are activated.The role of the KCTD16 in modulation of nociception and pain needs further experiments to fully understand its importance.This work was supported by