Temporal development of behavioral impairments in rats following locus coeruleus lesion induced by 6-hydroxydopamine: involvement of β3-adrenergic receptors.

Temporal development of behavioral impairments in rats following locus coeruleus lesion induced by 6-hydroxydopamine: involvement of β3-adrenergic receptors. Neuropharmacology. 2019 Apr 05;: Authors: Sampaio TB, Soares de Souza B, Roversi K, Schuh T, Poli A, Takahashi RN, Prediger RD Abstract Noradrenergic degeneration in the locus coeruleus (LC) seems a convergent neuropathological marker of different neurodegenerative diseases. Herein, we investigated the temporal development of apoptotic signaling activation in the LC, noradrenergic dysfunction and behavioral impairments in rats following the noradrenergic lesion of the LC. For this purpose, the dopamine reuptake inhibitor nomifensine was administered one hour before the stereotaxic bilateral injections of 6-hydroxydopamine (6-OHDA; 5, 10 or 20 μg/hem) into the LC. The behavioral and neurochemical analyses were performed at 7, 21 and 42 days after 6-OHDA injections. All doses of 6-OHDA induced neuronal death in LC, but only the highest dose (20 μg/hem) disrupted the motor function. 6-OHDA (5 μg/hem) injection induced short-term memory deficits in all periods, olfactory discrimination and long-term memory impairments at 7 days, and depressive-like behaviors at 21 and 42 days after injection. Moreover, 6-OHDA infusion increased Bax/Bcl2 ratio and caspase 3 levels, and decreased the dopamine β-hydroxylase immunocontent in the LC. Noradrenergic neurotransmission dysfunction was o...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research