Some regional anatomical relationships of TRH to 5-HT in rat limbic forebrain

It is now a recognized principle that various neuropeptides are neuronally co-localized with biogenic amine or aminoacid neurotransmitters. In the rat CNS it has previously been shown that TRH is co-localized with 5-HT (and also with substance P) in cell bodies of the posterior raphe that project to the spinal cord. Although TRH cell bodies are known to be widely distributed throughout the forebrain there is no other known co-localization with 5-HT. In this study we further specify the anatomical relationship of TRH with 5-HT by use of surgical and neurotoxic lesioning with reference to limbic forebrain regions wherein TRH is greatly increased following seizures. In groups of rats, the fimbria-fornix was lesioned alone, or combined with a lesion of the dorsal perforant path or the ventral perforant path. There was a sham lesioned control group. Additional groups were lesioned with 5, 7 dihydroxytryptamine, 100 μg i.v.t., 45 min. after i.p. desipramine, 25 mg/kg. All rats were sacrificed three weeks after lesions. Indoleamines were determined by HPLC in left anterior cortex, left pyriform/olfactory cortex, left dorsal hippocampus and left ventral hippocampus. TRH was determined by specific RIA in the corresponding right brain regions. The modal n was 7 rats. The surgical lesions reduced 5-HT to below the detection limit in dorsal hippocampus in all three groups, and to 31-52% of control in all the ventral hippocampus groups. 5-HIAA was reduced to 19-37% of control in dorsal and to 30-51% of control in ventral hippocampus. TRH was reduced to 44-61% of control in dorsal hippocampus and to 48-53% of control in ventral hippocampus. As was repeatedly observed in our previous reports all TRH levels in ventral hippocampus were higher than in dorsal hippocampus. The 5, 7 dihydroxytryptamine treatment nearly eliminated the indoleamines from all the forebrain regions examined while TRH levels were unchanged. These results can be explained by our previous data showing that immunoreactive TRH is intrinsic and localized to the vicinity of both CA and dentate granule cells of the hippocampus, but about half of hippocampal TRH enters via fibers of the fimbria-fornix. The perforant path appears to contribute no TRH to hippocampus, but, results with the combined lesion groups showed some reduction of 5-HIAA in ventral hippocampus as is expected from the known perforant path contribution of 5-HT. Since the neurotoxic lesion had no effect on TRH, the 5-HT pathway through the fimbria-fornix is probably anatomically separate from a parallel TRH pathway there. This study shows that co-localization of TRH with 5-HT is very unlikely in four specific limbic forebrain regions.