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

Summary

GABAB receptors, which are part of the brain's inhibitory system, are modulated by accessory proteins called KCTD16. In experiments using mice lacking the KCTD16 gene, baseline pain sensitivity and nerve cell activity in the spinal cord were similar to normal mice. However, when treated with the GABAB receptor agonist baclofen, normal mice showed greater pain relief (higher thresholds for heat and touch) than mice lacking KCTD16. In a model of peripheral inflammation, KCTD16-deficient mice tended to have higher pain thresholds, and baclofen's inhibitory effect on nerve signals was reduced. The findings suggest KCTD16 may be important for pain modulation during pathological conditions when GABAB receptors are activated, but further research is needed.

Study at a glance

Abstract

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