Intracerebral fetal raphé implants normalize hippocampal function but not cerebrovascular control in serotonin-depleted adult rat brain

Abstract

The effects of hypercapnia upon local cerebral blood flow and local cerebral glucose utilization were measured by quantitative autoradiography in parallel groups of rats (six per group) which 14–16 weeks previously had been treated with the serotonergic neurotoxin, methylenedioxymethamphetamine, followed by implantation of fetal raphé or basal forebrain tissues. Following the experiments, transplants were visualized by acetylcholinesterase histochemistry, and serotonergic reinnervation assessed using [ 3H]paroxetine binding to serotonin reuptake sites. In methylenedioxymethamphetamine-treated rats, contralateral to the implants, [ 3H]paroxetine binding was reduced by between 50 and 90% in the neocortex and hippocampus. Hippocampal glucose utilization was significantly increased in these rats, and the normal increase in flow which accompanies hypercapnia was also significantly enhanced. High levels of [ 3H]paroxetine binding were found within the raphé transplants (308±13 fmol/mg tissue). In host brain adjacent to the implant, binding levels were normalized, and in these same areas glucose utilization was also normalized. Basal forebrain implants had no effect upon either [ 3H]paroxetine binding or glucose utilization. Raphé transplants did not, however, alter the enhanced cerebrovascular response to hypercapnia induced by methylenedioxymethamphetamine, even in those areas where there was evidence of serotonergic reinnervation. The transplants also showed the same enhanced response. In conclusion, intracerebral fetal raphé implants normalize hippocampal function but not cerebrovascular control in serotonin-depleted adult rat brain, and despite not sharing the serotonergic deficit, blood flow in the implants follows that of the dysfunctional host.