Modulation of 5-hydroxytryptamine release in hippocampal slices of rats: Effects of fimbria-fornix lesions on 5-HT1B-autoreceptor and alpha(2)-heteroreceptor function

Fimbria-fornix lesions disrupt important parts of serotonergic and noradren ergic hippocampal afferents and elicit sprouting of sympathetic fibers from the superior cervical ganglion. Since B-hydroxytryptamine (5-HT) release i n the hippocampus is modulated by 5-HT1B auto- and alpha(2)-heteroreceptors , we investigated whether such lesions may alter these presynaptic mechanis ms. Hippocampal slices of sham-operated (SHAM) and fimbria-fornix-lesioned (LES) rats (14 months after surgery) were preincubated with [H-3]5-HT, supe rfused continuously, and stimulated electrically using two stimulation cond itions: either (a) 360 pulses 3 Hz, or (b) 20 pulses 100 Hz (2 ms, 28 mA, 4 V/chamber). The amount of [H-3]5-HT taken up by slices from LES rats was s ignificantly reduced, whereas the evoked 5-HT release (in percent of tissue -H-3) was unchanged compared to that of SHAM rats. The 5-HT1B agonist CP 93 ,129 or the alpha(2)-agonist UK 14,304 reduced the evoked 5-HT release more potently in slices from LES rats, but only using stimulation condition (a) , which permits inhibition by endogenously released transmitters. In LES ra ts, the facilitatory effect of the 5-HT antagonist metitepine was weaker, w hereas that of the alpha(2)-antagonist idazoxane was more pronounced than i n SHAM rats. In LES rats, hippocampal 5-HT content was reduced to about 45% of SHAM levels, whereas that of noradrenaline was increased by about 30% ( high-performance liquid chromatography). We conclude: (1) despite LES-induc ed changes in tissue levels of endogenous ligands, there is no down- or upr egulation of 5-HT1B-autoreceptors or alpha(2)-heteroreceptors on serotonerg ic neurons in the denervated rat hippocampus. (2) The reduced endogenous au toinhibition (by 5-HT) seems to be compensated for by an increased heteroin hibition (by noradrenaline). (C) 1999 Elsevier Science Inc.