Locus coeruleus lesions and resistance to extinction of a classically conditioned response: involvement of the neocortex and hippocampus.

Bilateral electrolytic lesions of the locus coeruleus were made in rabbits prior to classical conditioning of the nictitating membrane (NM) response. After recovery, the animals received one session of unpaired training followed by 3 days of paired acquisition training and 4 days of unpaired training (extinction). At the end of extinction norepinephrine (NE) and dopamine (DA) levels were measured in several brain regions. Each lesioned animal was placed into one of two groups according to whether or not the animal exhibited a significant depletion of cortical/hippocampal NE. A third group was formed by non-lesioned controls. There were no significant differences between the 3 groups during acquisition; however, during days 3 and 4 of unpaired extinction the group with cortical/hippocampal NE depletion showed significantly larger NM responses on the conditioned stimulus-alone trials than either of the two control groups. This extinction deficit appeared mainly in the unconditioned stimulus-period component of the tone-alone conditioned responses. The magnitude of the extinction deficit was highly correlated with the depletion of NE in both cortical and hippocampal samples but not with the depletion of NE in the hypothalamus/mid-thalamus, or cerebellum.