Locus coeruleus activity in perinatally protein-deprived rats: effects of fluoxetine administration.
We have previously described an increased locus coeruleus activity in perinatally protein-deprived rats. Since locus coeruleus dysfunction has been involved in different types of anxiety disorders and considering the modulating action of serotonergic transmission on locus coeruleus activity, we assessed the effect of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on locus coeruleus activity as measured by the firing rate and the number of spontaneously active cells/track. Repeated fluoxetine administration reduced locus coeruleus activity in both control and protein-deprived rats, although the reduction was greater in protein-deprived rats. Dose-response curves for the inhibitory effect of clonidine showed subsensitivity of alpha2-adrenergic autoreceptors in protein-deprived rats, a phenomenon reversed by fluoxetine treatment. Dose-response curves for the inhibitory effect of 2,5-dimethoxy-4-iodoamphetamine (DOI) were similar in both groups of rats. Following fluoxetine administration, subsensitivity to this effect developed in control but not in protein-deprived rats. Extracellular noradrenaline level in the prefrontal cortex, as measured by microdialysis procedure, was higher in protein-deprived rats compared to controls, and this difference was reduced after fluoxetine administration. A challenge with yohimbine increased the extracellular noradrenaline level in control but not in protein-deprived rats, suggesting subsensitivity of alpha2-adrenergic autoreceptors in early protein malnourished animals. These results stress the complexity of plastic changes induced by early protein malnutrition and sustain the hypothesis that perinatally protein-deprived rats may represent a useful animal model for screening antipanic agents.
Sodero
Alejandro O
AO
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, 5016, Córdoba, Argentina.
Valdomero
Analía
A
Cuadra
Gabriel R
GR
Ramírez
Oscar A
OA
Orsingher
Otto A
OA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D008125:Locus Coeruleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011502:Protein-Energy Malnutrition / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000662:Amphetamines; D018687:Antidepressive Agents, Second-Generation; D015306:Biogenic Monoamines; D003000:Clonidine; D005473:Fluoxetine; D009638:Norepinephrine; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D015016:Yohimbine; C079285:2,5-dimethoxy-N,N-dimethyl-4-iodoamphetamine