BURST STIMULATION OF THE MEDIAL FOREBRAIN-BUNDLE SELECTIVELY INCREASES FOS-LIKE IMMUNOREACTIVITY IN THE LIMBIC FOREBRAIN OF THE RAT

The present study was designed to evaluate the postsynaptic functional consequences of different presynaptic activity patterns in midbrain d opamine systems using electrical stimulation of the rat medial forebra in bundle and subsequent determination of c-fos expression, used as a marker for neuronal activation, in dopamine target areas, by means of Fos immunohistochemistry. Nerve terminal dopamine release evoked by el ectrical stimulation of the medial forebrain bundle was monitored in t he same animals using in vivo voltammetry. A 5 Hz stimulation consisti ng of 60 trains of five pulses and lasting I min was applied to the me dial forebrain bundle, This stimulation was repeated 15 times every 3 min. Its pattern was defined by the interpulse interval which was eith er 70 ms or 200 ms for burst or regularly spaced stimulation, respecti vely. Our results show that burst stimulation of the medial forebrain bundle, which increases release of dopamine in target areas, increases the basal Fos-like immunoreactivity in the stimulated hemisphere, whi le regular stimulation does not affect expression of this protein. Mor eover, the increase in Fos-like immunoreactivity induced by burst stim ulation is restricted to limbic related structures, i.e. nucleus accum bens shell and intermediate aspect of the lateral septum, and the majo r island of Calleja, but is not observed in motor related structures ( nucleus accumbens core and striatum). Pretreatment with the D-1 dopami ne receptor antagonist, SCH23390 (0.1 mg/kg, i.p.), blocked the increa se in Fos-like immunoreactivity induced by burst stimulation of the me dial forebrain bundle, suggesting a role for these receptors in the ob served effects. Pretreatment with the 5-hydroxytryptamine(2A/2C) recep tor antagonist ritanserin (0.4 mg/kg, i.p.) did not affect the increas e in Fos-like immunoreactivity induced by burst stimulation in the nuc leus accumbens shell or in the lateral septum, although it blocked the stimulated enhancement of Fos-like immunoreactivity in the major isla nd of Calleja. The present data indicate that, rather than the absolut e mean discharge rate of midbrain dopamine neurons, the temporal organ ization of the action potentials they generate conveys information to their target areas.