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The effects of intracerebral microinjections of neurotensin and xenopsin on self-stimulation of the medial prefrontal cortex of the rat were studied. Unilateral microinjections into the medial prefrontal cortex of neurotensin at doses of 0.625, 1.25, 2.5, 5 and 10 nmol produced a dose-related decrease of self-stimulation in the ipsilateral medial prefrontal cortex. Self-stimulation of the contralateral medial prefrontal contex, used as control, was not affected by the microinjections. Similar results were found with the neurotension-like octapeptide, xenopsin. Unilateral microinjections of xenoposin into the medial prefrontal cortex, at doses of 1.8, 3.6, 7.2 and 14.4 nmol produced a dose-related decrease of self-stimulation of the ipsilateral medial prefrontal cortex. Self-stimulation of the contralateral medial prefrontal cortex was not affected. These results suggest that neurotensin is part of the neurochemical substrate of self-stimulation in this cortical area.

Intracerebral microinjections of neurotensin (NT) decrease intracranial self-stimulation (ICSS) of the medial prefrontal cortex (MPC) in the rat. This effect could be due to the ability of NT to bind dopamine. To test this hypothesis we studied the effects of intracerebral microinjections of neuromedin N, a natural NT analogue that does not bind dopamine, on ICSS of the rat MPC. Unilateral microinjections of neuromedin N into the MPC at doses of 2.5, 5, 10, 20 and 40 nmol produced a dose-related decrease in ICSS of the ipsilateral MPC. ICSS of the contralateral MPC, used as a control, was not affected by the microinjections. These results suggest that the inhibitory effect of NT on ICSS is independent of NT-dopamine binding. Because neuromedin N is also present in the MPC, these results also suggest a possible neuromodulatory role of this neuropeptide on ICSS of the prefrontal cortex.