INTRACEREBRAL FETAL RAPHE IMPLANTS NORMALIZE HIPPOCAMPAL FUNCTION BUTNOT CEREBROVASCULAR CONTROL IN SEROTONIN-DEPLETED ADULT-RAT BRAIN

The effects of hypercapnia upon local cerebral blood flow and local ce rebral glucose utilization were measured by quantitative autoradiograp hy in parallel groups of rats (six per group) which 14-16 weeks previo usly had been treated with the serotonergic neurotoxin, methylenediosy methamphetamine, followed by implantation of fetal raphe or basal fore brain tissues. Following the experiments, transplants were visualized by acetylcholinesterase histochemistry, and serotonergic reinnervation assessed using [H-3]paroxetine binding to serotonin reuptake sites. I n methylenedioxymethamphetamine-treated rats, contralateral to the imp lants, [H-3]paroxetine binding was reduced by between 50 and 90% in th e neocortex and hippocampus. Hippocampal glucose utilization was signi ficantly increased in these rats, and the normal increase in flow whic h accompanies hypercapnia was also significantly enhanced. High levels of [H-3]paroxetine binding were found within the raphe transplants (3 08 +/- 13 fmol/mg tissue). In host brain adjacent to the implant, bind ing levels were normalized, and in these same areas glucose utilizatio n was also normalized. Basal forebrain implants had no effect upon eit her [H-3]parosetine binding or glucose utilization. Raphe transplants did not, however, alter the enhanced cerebrovascular response to hyper capnia induced by methylenedioxymethamphetamine, even in those areas w here there was evidence of serotonergic reinnervation. The transplants also showed the same enhanced response. In conclusion, intracerebral fetal raphe implants normalize hippocampal function but not cerebrovas cular control in serotonin-depleted adult rat brain, and despite not s haring the serotonergic deficit, blood Bow in the implants follows tha t of the dysfunctional host. (C) 1998 IBRO. Published by Elsevier Scie nce Ltd.