Administration of 8‐Hydroxy‐2‐(Di‐n‐Propylamino)tetralin in Raphe Nuclei Dorsalis and Medianus Reduces Serotonin Synthesis in the Rat Brain: Differences in Potency and Regional Sensitivity

Abstract

Following administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.04-5.0 micrograms/0.5 microliter) in the raphe nucleus dorsalis (DR) or medianus (MR), the synthesis of serotonin (5-HT), as assessed by the accumulation of 5-hydroxytryptophan (5-HTP) after decarboxylase inhibition, was measured in various regions of the rat CNS. At all doses, 8-OH-DPAT in the DR significantly reduced 5-HTP accumulation in the striatum, nucleus accumbens, cortex, and prefrontal cortex, whereas even the highest dose had no effect in the hippocampus, hypothalamus, and spinal cord. One microgram of 8-OH-DPAT in the MR significantly reduced 5-HTP accumulation in the nucleus accumbens and prefrontal cortex, and 5 micrograms had an effect in all the areas except the striatum and spinal cord. One and 5 micrograms of 8-OH-DPAT, administered in either the DR or MR, did not significantly modify the accumulation of dihydroxyphenylalanine in the striatum and nucleus accumbens. The results confirm that DR and MR have different sensitivities to 5-HT1A receptor agonists, and that activation of 5-HT1A receptors in these nuclei produces different effects on 5-HT synthesis in different brain regions.

Opposing actions of 5HT1A and 5HT2-like serotonin receptors on modulations of the electric signal waveform in the electric fish Brachyhypopomus pinnicaudatus

“…Autoreceptor activation leads to reduced neuronal firing and thus reduced 5-HT activity in the brain (Invernizzi et al, 1991;Sharp et al, 1989;VanderMaelen et al, 1986) whereas post-synaptic 5HT 1A activation mediates behavioral effects of brain 5-HT (Carey et al, 2005;Rabiner et al, 2004). Half of the fish that were given 8-OH-DPAT at [0.25 mM] enhanced their amplitudes and the other half in this group reduced theirs after injection, raising the possibility that both types of Not all drugs we used cross the blood-brain barrier to the same extent.…”

Galanin Is a Potent In Vivo Modulator of Mesencephalic Serotonergic Neurotransmission

“…The effects of galanin on TrpH, the rate-limiting enzyme in the biosynthesis of 5-HT (Lovenberg et al 1967) likely that the inhibition of TrpH enzyme activity by galanin is indirectly mediated by the inhibition of the raphe cell firing similarly to 5-HT 1A receptor agonists (Invernizzi et al 1991).…”

β-blocker Binding to Human 5-HT1A Receptors in vivo and in vitro Implications for Antidepressant Therapy

“…And thirdly, a dose of pindolol which blocks the 5-HT 1A autoreceptor might be expected to also block the postsynaptic 5-HT 1A receptor, potentially counteracting any antidepressant effect. Post-synaptic 5-HT 1A receptors are located in cortical and limbic areas (Peroutka 1985;Pazos et al 1988), where they mediate the effects of 5-HT released from the nerve terminals Chaput et al 1991;Invernizzi et al 1991;Sinton and Fallon 1988).…”

“…And thirdly, a dose of pindolol which blocks the 5-HT 1A autoreceptor might be expected to also block the postsynaptic 5-HT 1A receptor, potentially counteracting any antidepressant effect. Post-synaptic 5-HT 1A receptors are located in cortical and limbic areas (Peroutka 1985;Pazos et al 1988), where they mediate the effects of 5-HT released from the nerve terminals Chaput et al 1991;Invernizzi et al 1991;Sinton and Fallon 1988).Two other ␤ -blockers, penbutolol and tertatolol, also display nanomolar affinity for the 5-HT 1A receptor in rodent brain (Prisco et al 1993;Jolas et al 1993;Hjorth and Sharp 1993). In rat microdialysis studies penbutolol and tertatolol reliably increase the levels of extracellular 5-HT, unlike pindolol in some studies (Gartside et al 1999), when co-administered with an SSRI.…”