VENTRAL PALLIDUM SELF-STIMULATION INDUCES STIMULUS-DEPENDENT INCREASEIN C-FOS EXPRESSION IN REWARD-RELATED BRAIN-REGIONS

Neuronal expression of Fos, the protein product of the immediate early gene c-fos has been used as a high resolution metabolic marker for ma pping polysynaptic pathways in the brain. We used Fos immunohistochemi stry to reveal neuronal activation following self-stimulation of the v entral pallidum. Four groups of rats were allowed to self-stimulate fo r 30 min with 0.4 a trains of cathodal rectangular pulses of constant intensity (0.4 mA) and duration (0.1 ms). Each group was assigned a di fferent pulse frequency, (3, 17, 24 and 50 pulses/stimulation train), which was preselected from within each animal's rate-frequency functio n. The subjects that were assigned three pulses failed to self-stimula te and were considered as controls. The subjects that were assigned 17 pulses self-stimulated at half-maximal rate, whereas those that were assigned 24 and 50 pulses self-stimulated at maximal rates. The animal s were sacrificed 90 min after the self-stimulation session and their brains were processed for Fos-like immunoreactivity. Fos-like immunore activity was found to increase as a function of pulse frequency in sev eral brain regions known to be involved in drug and/or brain stimulati on reward (medial prefrontal cortex, lateral septum, nucleus accumbens , lateral hypothalamus and ventral tegmental area), whereas it was not affected in structures devoid of such involvement (substantia nigra r eticulata and dorsolateral striatum). The level of Fos expression indu ced by trains of 50 pulses was considerably higher than that produced by 24 pulses although both frequencies supported the same (maximal) se lf-stimulation rate. This finding indicates that Fos expression correl ated with reward magnitude (known to increase between these frequencie s), not with bar-pressing rate, thus suggesting the presence of a rewa rd-specific effect. The finding of a frequency-dependent Fos expressio n in a behavioural paradigm can be considered analogous to a pharmacol ogical dose-response curve and, as such, our results may open new aven ues for the use of Fos immunohistochemistry in quantitative neurobehav ioural studies.