Functional topography of brain serotonergic pathways in the rat

Abstract

Objectives: The aims of the present series of experiments were [1] to study functional subdivisions within the two major ascending serotonergic projections originating in the dorsal and the median raphe nuclei of the brainstem in the rat, [2] to investigate the functional coupling of somato-dendritic autoreceptors, and to examine [3] the role played by brain 5-HT1A receptors by means of the selective agonist 8-OH-DPAT.

Methods: In order both to separate effects mediated by the two ascending serotonergic raphe projections and to separate pre- and post-synaptic effects, 5-HT and 8-OH-DPAT were locally applied into the cell body regions and into projection areas. Using stereotaxic procedures, guide cannulas were fixed to the skull bone with dental cement in deeply anaesthetized adult male Wistar rats. The animals were allowed one week of recovery after which the behavioral and biochemical effects of localized injections of 5-HT (10 or 40 micrograms) or of 8-OH-DPAT (1 or 5 micrograms) were studied. The behavioral functions observed were sexual behavior, spontaneous motor activity, treadmill locomotion and core temperature. In addition, the effects of localized raphe injections of 5-HT or 8-OH-DPAT on forebrain monoamine synthesis were investigated by measuring the accumulation of 5-HTP and DOPA following inhibition of aromatic L-amino acid cerebral decarboxylase.

Results: Localized 5-HT injections into the DR, but not into the MR, produced a decrease in core temperature, whereas an injection into either nucleus produced a facilitation of ejaculatory behavior. Spontaneous motor activity was increased and decreased by the MR and DR injections, respectively. The forebrain 5-HT synthesis was decreased by injections into the DR whereas no effects were observed after injections into the MR. These effects, obtained by 5-HT injections into the somato-dendritic region of the serotonergic neurons, indicate a functional role for autoreceptors. The observation that forebrain 5-HT injections produced effects on sexual and motor behaviors opposite to those produced by raphe injections, support the presence of inhibitory coupled autoreceptors in the mediation of these functions. Localized raphe injections of 8-OH-DPAT produced the same effects as 5-HT on core temperature and on spontaneous motor activity, although the effects of MR injections were relatively stronger in this case. Ejaculatory behavior was affected by MR, but not DR, injections. Forebrain 5-HT synthesis was markedly affected by MR injections whereas DR injections produced more modest effects.

Conclusions: The results obtained using localized 5-HT injections into the rat brain suggest a specific role for ascending DR projections in thermoregulatory mechanisms. Motor activity measurements indicate distinct and different roles for ascending DR and MR serotonergic projections, whereas both projections work together in the mediation of male rat ejaculatory behavior. Autoregulation of forebrain 5-HT synthesis appears to be considerably stronger in the DR than in the MR. The experiments with 8-OH-DPAT suggest that serotonergic mechanisms in thermoregulation are mediated via receptors of the 5-HT1A type. The 8-OH-DPAT-induced effects on sexual behavior, spontaneous motor activity and on forebrain 5-HT synthesis suggests a specific functional role for 5-HT1A receptors in the MR.