The effects of cirazoline on the firing rates of thermally classified neurons in the anterior hypothalamus of the rat

Abstract

Peripheral exposure to LPS induces a biphasic fever thought to be initiated via vagal afferents to the anterior hypothalamus (AH), an important thermoregulatory control center in the brain. Previous studies have shown norepinephrine (NE) synaptically mediates this Prostaglandin E2 (PGE2)-dependent change in temperature through the selective activation of α-2 adrenoreceptors (AR). However, there is clear evidence that α-1 AR activation of thermoregulatory hypothalamic neurons will result in a rapid hyperthermia that is not dependent on PGE2. This direct action of NE in the AH was tested in the present study by recording the single-unit activity of these neurons in a tissue slice preparation from the adult male rat, in response to temperature and the selective α-1 AR agonist Cirazoline (10–100 μM). Neurons in the AH were classified as either warm-sensitive (m ≥ 0.8 impulses.s−1.°C−1), or temperature-insensitive. Warm-sensitive neurons responded to cirazoline with a decrease in firing rate, while temperature-insensitive neurons showed an initial firing rate increase. These responses are similar to those reported for PGE2 and suggest that both warm-sensitive and temperature-insensitive neurons in the AH are important in mediating this α-1 AR-dependent hyperthermic shift in body temperature. (Supported by NSF: IBN-9983624, NIH: NS053794 and a HHMI grant to the College of William and Mary.)