Evidence that noradrenergic neurons in the A1 and A2 nuclei are lesioned by low doses of 6-OHDA injected into the locus coeruleus

In order to determine the specificity of a lesion aimed at the locus coeruleus (LC), various doses of 6-hydroxydopamine (6-OHDA), a neurotoxin which selectively lesions catecholaminergic neurons, were bilaterally infused into the LC. The noradrenaline (NA) concentration in the frontal cortex, hippocampus, hypothalamus, LC, A1 and A2 nuclei decreased with increasing doses of 6-OHDA. A 1 μg dose of 6-OHDA injected bilaterally into the LC caused maximal depletion of the NA concentration in the frontal cortex, hippocampus and A1 and A2 nuclei. A dose of 2 μg 6-OHDA caused further depletion of the NA content of the hypothalamus and LC. These findings suggest that A1 and A2 neurons which project to the hypothalamus may have been lesioned or that the noradrenergic projection from the LC to the hypothalamus may be greater than was previously suspected. Alternatively, leakage of 6-OHDA into the cerebrospinal fluid may have occurred at the higher doses, thus directly exposing the hypothalamus to the toxic effects of 6-OHDA.