Locus coeruleus and dorsal raphe neuron activity and response to acute antidepressant administration in a rat model of Parkinson's disease.
In addition to noradrenergic and serotonergic systems, dopaminergic neurotransmission seems to play an important role in the aetiopathogenesis of, and recovery from, depression. Moreover, the incidence of depression is higher in patients affected by diseases where the dopaminergic system is highly impaired, such us Parkinson's disease. Here, we investigated the effects of dopamine degeneration on the activity and response to antidepressants of locus coeruleus (LC) noradrenergic and dorsal raphe nucleus (DRN) serotonergic neurons. To this end, single-unit extracellular recordings were performed in control and 6-hydroxydopamine (6-OHDA)-lesioned animals. In this latter group, LC neurons showed a lower basal firing rate as well as less sensitivity to the administration of the serotonin reuptake inhibitor, fluoxetine. The rest of electrophysiological parameters and the response to the administration of the α2-adrenoceptor agonist, clonidine and the noradrenaline reuptake inhibitor, reboxetine remained unaltered. In the DRN, dopamine depletion did not modify the basal electrophysiological characteristics and the response to clonidine or fluoxetine administration. In contrast, the administration of reboxetine more efficiently induced an inhibitory effect in the lesioned group. In additional analyses it was observed that while in control animals, LC and DRN basal firing rate was significantly correlated, this relationship was lost after the 6-OHDA lesion. In conclusion, dopaminergic degeneration alters LC neuron basal activity, the relationship/synteny between both nuclei, and their response to antidepressants. These findings shed fresh light on our understanding of the role of dopamine in depression and the mechanism action of antidepressants.
Miguelez
Cristina
C
Department of Pharmacology, Faculty of Medicine and Dentistry, University of the Basque Country, Leioa, Vizcaya, Spain.
Grandoso
Laura
L
Ugedo
Luisa
L
D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D055724:Electrophysiological Phenomena / Q000187:drug effects; D008125:Locus Coeruleus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D016627:Oxidopamine / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000378:metabolism
D018663:Adrenergic Agents; D000928:Antidepressive Agents; D011941:Receptors, Adrenergic; D044282:Receptor, Serotonin, 5-HT1A; D016627:Oxidopamine