Central action of endogenous sugar acid (2-buten-4-olide): Comparison with local anesthesia in hypothalamus

Abstract

Rats were trained to discriminate cue tone stimuli (CTS) predicting reward (CTS +) [juice or intracranial self-stimulation (ICSS)], or aversion (CTS −) (mild electric shock or tail pinch). Unit activity in the lateral hypothalamus (LHA) and lateral preoptic-anterior hypothalamic area (1POA-AHA) of the rat was recorded during CTS learning. The effects of local anesthesia of the amygdala (AM), ventral tegmental area (VTA) or LHA by procaine hydrochloride, and the effects of intraperitoneal or intravenous 2-buten-4-olide (2-B4O) on LHA neural activity and licking behavior were compared. LHA neurons differentiated between rewarding and aversive stimuli, and acquired corresponding discrimination of CTS + and CTS −. In the 1POA-AHA, neurons responded similarly to CTS +, rewarding stimuli, CTS − and aversive stimuli. Procainization of the AM suppressed LHA neural responses to CTS1 + predicting juice, and stopped licking for juice. Procainization of the VTA suppressed LHA neural responses to CTS2 + predicting ICSS, and stopped licking for ICSS. LHA procainization suppressed both licking for juice and ICSS. Both intraperitoneal and intravenous 2-B4O stopped licking for juice and ICSS, but did not influence LHA responses to CTS1 + or CTS2 +. The results suggest that dynamic interaction of AM-LHA-VTA are important for CTS + learning, and 2-B4O acts directly on LHA neurons while maintaining afferent sensory inputs to the LHA.