Preliminary studies in our laboratory indicate that the gap junction protein Cx36 is expressed in neurones in the brainstem and spinal cord in areas associated with control of autonomic functions. These include nuclei with autonomic functions, such as the nucleus tractus solitarius and the intermediolateral cell column. This study examines how mefloquine, an anti-malarial drug that blocks Cx36 containing gap junctions (1), influences cardiorespiratory reflexes. 18 day old, male, Wistar rats were prepared for the working heart brainstem preparation (2) by anaesthetising with halothane (5% in O2) until loss of paw withdrawal reflex and then bisecting sub-diaphragmatically. The animal was decerebrated at the precollicular level and skinned. The dorsal surface of the brainstem was exposed by removal of the skull and cerebellum. Phrenic nerve discharge rate (PND), heart rate, perfusion pressure and sympathetic chain activity were recorded. Data is presented as means +/- standard errors and statistical analysis was conducted using ANOVA (p<0.05). The addition of mefloquine (MF) to the perfusate, at concentrations similar for treatment of malaria (1µM), significantly reduced responses to baroreceptor challenges compared to control (n=6, p<0.05); time for expiration (Te) decreased 11.19% (from 1.49s ± 0.17 to 1.27s ± 0.23) compared to 31.17% (from 2.47s ± 0.50 to 1.68s ± 0.36). Time of total expiration and inspiration (Ttot) decreased 12.32% (from 2.11s ± 0.21 to 1.84s ± 2.56), compared to 29.70% (from 3.31s ± 0.58 to 2.32s ± 0.42). The PND rate increase was18.45% (from 30.63 ± 3.08 to 36.28 ±4.02) compared to 54.65% in control (from 22.27 ± 3.46 to 34.44 ±6.41). MF increased baroreceptor reflex sensitivity, expressed as change in heart rate per change in perfusion pressure, from control values of 1.79 ± 0.26 to 4.08 ± 1.78. These studies indicate that in the WHBP mefloquine is associated with increased baroreceptor sensitivity and decreased changes to respiratory output. Future studies aim to examine how Cx36 gap junctions contribute to these actions at cellular and network levels.