Contrasting effects of dopamine antagonists and frequency reduction on Fos expression induced by lateral hypothalamic...

To help further identify the reward-relevant regions activated by electrical stimulation of the lateral hypothalamus, Fos expression was quantified in 23 brain regions in naïve, awake rats following non-contingent stimulation with a frequency that supports self-stimulation (100 Hz), a frequency that supports only minimal responding (50 Hz) and a frequency that does not support self-stimulation (25 Hz). Fos expression was also examined in stimulated and unstimulated rats pretreated with SCH 23390 (a dopamine D1 antagonist) or spiperone (a D2-like antagonist), at doses known to greatly inhibit responding for self-stimulation. Lowering the stimulation frequency from 100 to 50 Hz reduced Fos labelling in all areas, except for a few cells immediately surrounding the electrode tip. No differences were observed between unstimulated rats and those receiving 25 Hz stimulation. This suggests that a critical threshold of stimulation is required before other reward-relevant regions in the midbrain and forebrain are recruited with higher frequency stimulation. Pretreatment with SCH 23390 (0.1 mg/kg) inhibited stimulation-induced Fos expression in some key dopamine terminal areas, such as the nucleus accumbens (core and shell) and medial caudate-putamen, but not in directly driven neurons near the stimulation site. In contrast, spiperone (0.1 mg/kg) did not affect the pattern of stimulation-induced Fos expression, but induced immunolabelling in the dorsolateral caudate-putamen, an area associated with the extrapyramidal side-effects of antipsychotic drugs. These results reveal the utility of Fos immunohistochemistry to show how different treatments that alter the rewarding impact of electrical brain stimulation achieve their effects at the neural level.