A comparison of the effects of mesencephalic injections of neurotensin(1–13) and neuromedin N on brain electrical self-stimulation

Abstract

Neuromedin N (NM-N), a hexapeptide that shares a four amino acid C- terminal homology with the tridecapeptide, neurotensin (NT), has been suggested as a potential neurotransmitter or neuromodulator that could interact with the NT-sensitive receptors. In this experiment, we compared the effects of an equimolar concentration of NM-N and NT(1–13) injected in the ventral tegmental area (VTA) on brain electrical self-stimulation (SS), a behavior previously shown to be potentiated by VTA injections of NT(1–13). Rats implanted with a stimulating electrode in the mesencephalic central gray and a guide cannula in the VTA were trained to lever press to obtain rewarding electrical stimulations. Functions relating the rate of lever pressing to the stimulation frequency were determined, on separate daily tests, before and after the injection of 3 nmol of NM-N, NT(1–13), or an equal volume of saline vehicle. At this concentration, both NM-N and NT(1–13) produced a significant facilitation of SS when compared to saline vehicle, an effect that was not seen when the peptides were injected outside the VTA. The facilitation of SS by NM-N, however, was much weaker and of a shorter duration than the one produced by NT(1–13). The shorter time course and the weaker behavioral effect of NM-N compared to NT(1–13) are consistent with its lower potency at the NT receptor and its faster rate of enzymatic degradation in the VTA, and suggest that NM-N potentiated the reward-relevant neural signal by acting on mesencephalic NT receptors.