beta(2)-Adrenoceptor stimulation restores frontal cortex plasticity and improves visuospatial performance in hidden-prenatally-malnourished young-adult rats (Neurobiology Of Learning And Memory – ISI)

Patricio Sáez-Briones, Rubén Soto-Moyano, Héctor Burgos, Amparo Castillo, Luis Valladares, Carlos Morgan, Hernán Pérez, Rafael Barra, Luis Constandil, Claudio Laurido, Alejandro Hernández


Moderate reduction in dietary protein composition of pregnant rats from 25% to 8% casein, calorically compensated by carbohydrates, has been described as a ‘‘hidden malnutrition’’ because it does not alter body and brain weights of pups at birth. However, this dietary treatment leads to altered central nora­drenergic systems, impaired cortical long-term potentiation (LTP) and worsened visuo-spatial memory performance. Given the increasing interest on the role played by P2-adrenoceptors (P2-ARs) on brain plas­ticity, the present study aimed to address the following in hidden-malnourished and eutrophic control rats: (i) the expression levels of P2-ARs in the frontal cortex determined by immunohistochemistry, and (ii) the effect of the P2 selective agonist clenbuterol on both LTP elicited in vivo in the prefrontal cor­tex and visuospatial performance measured in an eight-arm radial maze. Our results showed that, prena­tally malnourished rats exhibited a significant reduction of neocortical P2-AR expression in adulthood. Concomitantly, they were unable to elicit and maintain prefrontal cortex LTP and exhibited lower visu- ospatial learning performance. Administration of clenbuterol (0.019, 0.038 and 0.075mg/kg i.p.) enhanced LTP in malnourished and control animals and restored visuospatial learning performance in malnourished but not in normal rats, in a dose-dependent manner. The results suggest that decreased density of neocortical P2-ARs during postnatal life, subsequent to hidden prenatal malnutrition might affect some synaptic networks required to elicit neocortical LTP and form visuospatial memory, since those neuroplastic deficits were counteracted by P2-AR stimulation.

Keywords: p2-Adrenoceptor, clenbuterol, long-term potentiation, prefrontal cortex, prenatal protein malnutrition, visuospatial performance.

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