||The orienting reflex (OR) may involve the locus coeruleus - norepinephrine pathway (LC-NE). For example, a role for the LC-NE in attention and vigilance has been hypothesized, and neurons in the LC-NE of awake animals respond best to salient sensory stimuli. Stimulation of the LC-NE slows heart rate and desynchronizes electroencephalogram (EEG) (Miyawaki, 1993; Berridge & Foote, 1991), which are two components of the orienting reflex . Rats were chronically implanted for electrocardiogram (EKG) and EEG recordings. The OR was elicited in rats by taped rat vocalizations or continuous tone stimuli in a sound attenuating chamber. Norepinephrine was depleted by single N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) injections (50 mg/kg, i. p.), a selective neurotoxin for the LC-NE, and tested for an OR 11 to 17 days after injection. Central NE levels in control and DSP4 treated animals were determined by HPLC with electrochemical detection. NE concentrations were significantly reduced by DSP4 lesions by 60.9% (p < 0.005) in hippocampus and 49.1% (p < 0.05) in parietal cortex. Reduction of NE concentrations in hypothalamus (47.1%) and frontal cortex (42.7%) were not significant. In control animals (n=10) there was a 7% decrease (p < 0.05) during the 60-second rat vocalizations and a 6.1% decrease (p < 0.05) during the 60-second continuous tone within ten seconds after the onset of these orienting stimuli, as compared to baseline heart rate (10 seconds before stimuli), and heart rate remained significantly decreased (p < 0.05) for 40 seconds. Some habituation was seen in both cases. In addition, log absolute power of alpha frequencies (8 and 9 Hz) in the EEG were also suppressed significantly (p < 0.05) after onset of rat vocalizations in control animals (n=8), comparing five seconds of post-stimulus activity to five seconds of pre-stimulus baseline activity. In contrast, in the DSP4 treated rats (n=10), showed a small, non-significant decrease in heart rate during both of the orienting stimuli. Also, no significant suppression in EEG alpha frequencies was seen during rat vocalizations (n=8). There were no significant differences between controls and DSP4 treatments in locomotor activity in an open-field test, although DSP4 treated animals spent more time in grooming behavior during the last five minute testing period as compared to the first five minute testing period. We conclude that there is a crucial involvement of LC-NE system in the orienting reflex of rats.