Increased neuronal activity in locus coeruleus from adult rats undernourished at perinatal age: its reversal by desipramine.
The spontaneous activity of locus coeruleus (LC) noradrenergic neurons was assessed by single unit recording in adult recovered rats undernourished at perinatal age as compared with wellnourished animals. Locus coeruleus activity, measured by the firing rate of noradrenergic neurons and the number of spontaneously active cells/track was significantly higher in deprived rats than in controls. In addition, dose-response curves for the inhibitory LC activity of clonidine showed a shift to the right in deprived animals indicating a subsensitivity of alpha2-adrenergic autoreceptors. This fact suggests an alteration in the negative feedback mechanism mediated by somatodentritic alpha2 autoreceptors that modulate the activity of LC neurons, and may account for the behavioral alterations attributed to early undernutrition. Repeated desipramine (DMI) administration to deprived rats reduced LC activity to values comparable to controls, which were not affected after a similar treatment. These data extend to previous reports on long-lasting or permanent plastic changes in the CNS induced by early undernutrition, which may be reverted by pharmacological manipulations. In addition, these results support the hypothesis that alterations induced by early undernutrition are in the same direction as and resemble those described for patients with panic disorders. Furthermore, together with behavioral alterations and selective anxiolytic effect of DMI and other drugs with antipanic effects described in early malnourished rats, the present data support the proposal that perinatally deprived rats may be a useful model for screening drugs with potential antipanic activity.
Nasif
F J
FJ
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina.
Ramírez
O A
OA
Cuadra
G R
GR
Orsingher
O A
OA
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D005260:Female; D008125:Locus Coeruleus / Q000187:drug effects / Q000503:physiopathology*; D023421:Models, Animal; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009748:Nutrition Disorders / Q000503:physiopathology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D003000:Clonidine; D003891:Desipramine