DOSE-DEPENDENT BEHAVIOURAL AND MEDIAL PREFRONTAL LOCAL-FIELD POTENTIAL EFFECTS OF PSILOCYBIN IN RATS

Head twitches and wet dog shakes are widely used as behavioural markers of psychedelic action via 5-HT2A receptor activation in rodents, yet their validity in rats remains unclear. Here, we assessed dose-dependent effects of psilocybin on these canonical behaviours and medial prefrontal cortex (mPFC) neural activity in young adult (9–12 weeks) male and female Lister Hooded rats.
For behavioural studies, rats received psilocybin (0.1, 1, or 3 mg/kg, i.p.) or saline in a within-subjects design. Head twitches, wet dog shakes, locomotion, grooming, and back twitches were measured in an open field for 2 h post-injection. In a separate cohort, the effects of psilocybin (1 or 3 mg/kg) on local field potentials and spiking activity across infralimbic and prelimbic mPFC were recorded under urethane anaesthesia using a 1×16 NeuroNexus multi-electrode array. Using a stimulation electrode placed in the ventral hippocampus (VH), we assessed VH–mPFC synaptic connectivity and short-term plasticity.Psilocybin did not increase head twitches or wet dog shakes at any dose. At 1 mg/kg, psilocybin increased locomotion, whereas 3 mg/kg reduced locomotion and grooming. Electrophysiological recordings revealed increased mPFC high-gamma (51–80 Hz) power during the first 30 min following psilocybin administration (1 or 3 mg/kg). Additional electrophysiology analyses are ongoing.
Our findings show that in young adult Lister Hooded rats, psilocybin does not elicit head twitches or wet dog shakes yet produces dose-dependent locomotor effects. Despite contrasting motor outcomes, both 1 and 3 mg/kg increased mPFC high gamma power, indicating mPFC engagement independent of canonical behavioural markers.