Modulation of acetylcholine and 5-hydroxytryptamine release in hippocampalslices of rats with fimbria-fornix lesions and intrahippocampal grafts containing cholinergic and/or serotonergic neurons

Three-month-old Long-Evans female rats sustained aspirative lesions of the dorsal septohippocampal pathways and, 2 weeks later, received intrahippocam pal suspension grafts containing fetal cells from the mesencephalic raphe ( rich in serotonergic neurons; RAPHE), the medial septum and the diagonal ba nd of Broca (rich in cholinergic neurons; SEPT), or a mixture of both (COTR ). Lesion-only (LES) and sham-operated rats (SHAM) were used as controls. H ippocampal slices of these rats (5-9 month after surgery) wore preincubated with [H-3]choline or [H-3]5-HT, superfused continuously (in the presence o f hemicholinium-3 or fluvoxamine) and stimulated electrically (360 pulses, 2 ms, 3 Hz, 26-28 mA) in order to study the presynaptic modulation of acety lcholine (ACh) and serotonin (5-HT) release. The accumulation of [H-3]choli ne and the evoked overflow of [H-3]ACh were significantly reduced in slices from LES and RAPHE rats, but reached a close-to-normal level in SEPT and C OTR rats. As to accumulation and overflow of [H-3]5-HT, the lesion-induced reduction was compensated for only in RAPHE and COTR rats. The relative amo unt of evoked [H-3]5-HT release (in % of tissue-H-3) was significantly incr eased in LES and SEPT rats. Only slight differences (group LES) were found in the sensitivity of muscarinic and serotonergic autoreceptors towards oxo tremorine and CP 93,129, respectively. Moreover, CP 93,129 induced a signif icantly weaker inhibition of ACh release in slices of COTR rats than in all other groups. Using the 5-HT1A receptor agonist 8-OH-DPAT and antagonist W ay 100,635, no evidence for a modulatory influence of 5-HT1A receptors was found in RAPHE and COTR rats. It is concluded that despite substantial lesi on- and graft-induced changes in the amount of ACh and 5-HT released by hip pocampal slices of lesion-only or grafted rats, the presynaptic modulation of these transmitters is only slightly affected by changes in the neuronal environment. (C) 1999 Elsevier Science Inc.