Regional differences in desensitization of c-Fos expression following repeated self-stimulation of the medial forebrain bundle in the rat

The acute self-stimulation of the medial forebrain bundle was reported to i nduce the expression of c-Fos, the protein product of c-fos, an immediate e arly gene, in the central nervous system. In the present study, we examined regional changes in c-Fos expression in several reward-related areas of ra t brain in response to short- and long-term exposure to self-stimulation of the medial forebrain bundle. Short-term one-hour stimulation of the medial forebrain bundle for one day after training, which evoked steady self-stim ulation behavior, significantly increased the number of c-Fos-positive neur ons bilaterally in all of 15 brain structures assayed, as compared to the n on-stimulation control. Among them, structures showing a larger number of t he stained neurons on the stimulated side were the anterior olfactory nucle us, amygdala, medial caudate-putamen complex, lateral septum, bed nucleus o f the stria terminals, ventral pallidum, substantia innominata, lateral pre optic area, medial preoptic area, lateral hypothalamus rostral to the stimu lating electrodes, and substantia nigra. Long-term stimulation of the media l forebrain bundle once daily for five successive days, which maintained co nsistently stable self-stimulation behavior, also increased the number of c -Fos-positive neurons in the aforementioned structures, as compared to the control. However, the long-term rewarding stimulation diminished the increa sed number of labeled neurons, as compared to the short-term rewarding stim ulation. Seven areas, medial caudate-putamen complex, ventral pallidum, sub stantia innominata, lateral preoptic area, medial preoptic area, rostral la teral hypothalamus and substantia nigra, showed asymmetrical, ipsilateral p redominance after the short- and long-term stimulation. However, the staine d neuron count in those areas after the long-term stimulation was reduced t o less than 50% of that found after the short-term stimulation with the exc eption of lateral preoptic area and rostral lateral hypothalamus. The results suggest that the development of desensitization of c-Fos respon se may differ among the reward-relevant brain regions as a consequence of r epeated self-stimulation. They also indicate that a larger portion of neuro ns in the lateral preoptic area and rostral lateral hypothalamus may be imp licated in both short- and long-term self-stimulations of the medial forebr ain bundle. (C) 1999 IBRO. Published by Elsevier Science Ltd.