Brain dialysis: changes in the activities of dopamine neurons in rat striatum by perfusion of acetylcholine agonists under freely moving conditions

A dialysis cannula implanted into rat striatum was perfused with Ringer's solution containing drugs. Levels of 3,4-dihydroxyphenyl-acetic acid (DOPAC) and homovanillic acid (HVA) in the dialysate or striatal tissue were determined by HPLC with electrochemical detection. Continuous perfusion of oxotremorine, a muscarinic agonist, for 4 h gradually increased the levels of DOPAC and HVA. The maximal levels of DOPAC and HVA were 180 and 130% of the basal ones, respectively. Perfusion of lobeline, a nicotinic agonist, caused a rapid increase in DOPAC level within I h (160% of the basal level) and HVA was 120% of the basal level for 4 h. In striatal tissue 20 min after starting perfusion of oxotremorine or lobeline, there were no changes in DOPAC and HVA measured except for a decrease in dopamine after lobeline. Pretreatment with tetrodotoxin suppressed the effect of oxotremorine, but did not suppress the effect of the lobeline. These data suggest that, in the rat striatum in vivo, most of the muscarinic receptors indirectly enhance the turnover of dopamine via striatonigral or other loops, while some of the nicotinic receptors directly enhance the release or turnover of dopamine in the dopamine nerve terminals.