243. FIBROBLAST GROWTH FACTOR 2 MODULATES CENTRAL MONOAMINERGIC NEURONS <i>IN VIVO</i>

Abstract Background Fibroblast growth factor 2 (FGF2) has been implicated in modulating mood and addiction-related behaviors (Elsayed et al Biol Psychiatry 72:258, 2012). Previous studies have reported both anxiolytic and antidepressant-like effects of FGF2 as well as its potential pro-addictive effects (Even-Chen et al J Neurosci 37:8742, 2017). Given the critical role of central noradrenergic neurons in regulating mood, stress response, and arousal, it is plausible that FGF2 influences these behaviors via modulation of noradrenergic neuronal activity in the locus coeruleus (LC). However, the effects of FGF2 on the firing patterns of LC noradrenergic neurons remain poorly understood. Aims &amp; Objectives This study aimed to investigate the effect of recombinant FGF2 on the excitability and firing patterns of noradrenergic neurons in the LC of male and female rats, with a focus on burst firing activity. Method Adult male and female Wistar rats were randomly divided into two groups. The first group received subcutaneous (s.c.) injection of FGF2 (80 μg/kg), and the second group received vehicle. One-hour post-injection, rats were anesthetized with chloral hydrate (0.4 g/kg, intraperitoneally) and placed in a stereotaxic frame. The electrode was lowered into the LC. Noradrenergic neurons were identified based on their characteristic firing patterns and action potential waveforms (Even-Chen et al J Neurosci 39:7947, 2019). Spontaneous firing activity was recorded for at least 3 minutes per neuron. The firing rate, burst frequency, and percent of spikes within bursts were analyzed for sex- and treatment-related differences. Results FGF2 significantly influenced the activity of noradrenergic neurons in the LC. The mean firing rate and burst frequency of LC neurons showed significant sex-related differences (F[1,147]=11.33, p&amp;lt;0.001 and F[1,128]=6.11, p=0.02, respectively), with males exhibiting higher values than females. Additionally, a significant interaction between sex and FGF2 treatment was observed for the percent of spikes within bursts (F1,128=3.98, p=0.048). Post-hoc analysis indicated that the firing rate was higher in males compared to females in both vehicle-treated (p=0.04) and FGF2-treated groups (p=0.007). Notably, sex-related differences in burst frequency (p=0.02) and percent of spikes within bursts (p=0.01) were evident only in the FGF2-treated rats. Moreover, FGF2 increased the percent of spikes within bursts in males by 130% compared to vehicle-treated rats (p=0.03), whereas no such effect was observed in females. Discussion &amp; Conclusions Our findings demonstrate that FGF2 enhances the burst firing activity of LC noradrenergic neurons, with pronounced sex differences in its effects. The ability of FGF2 to increase the percent of spikes within bursts in males suggests that it may selectively potentiate noradrenergic transmission in a sex-dependent manner. These results provide new insights into the role of FGF2 in modulating the central noradrenergic system and its potential implications for mood and arousal regulation. This work was supported by the grants APVV-20-0202, APVV-22-0061, VEGA-2/0057/22, and VEGA-2/0045/24.