Antidepressants and brain monoaminergic systems: a dimensional approach to understanding their behavioural effects in depression and anxiety disorders.
A series of experiments were carried out in which the single unit activity of presumed noradrenergic (NE) neurons in the area of the locus coeruleus (LC) was examined in freely moving cats during two conditioning paradigms and in response to pharmacologic manipulations relevant to anxiety. LC unit activity was examined during conditioned emotional response (CER) and conditioned food reward (CFR) training. During CER training, LC units showed a large increase in activity in response to a stimulus paired with a noxious air puff, whereas no increase in unit activity was seen in response to a stimulus not paired with the air puff (both comparisons relative to their appropriate control conditions). By contrast, during CFR training, a stimulus paired with a rewarding food delivery did not elicit a significant increase in LC unit activity relative to its appropriate control condition. Therefore, NE units in the LC greatly increase their activity in response to a stimulus that predicts the occurrence of a noxious event, but not in response to a stimulus that predicts the occurrence of a rewarding event. Administration of the anxiolytic drug diazepam (0.25 and 2.0 mg/kg, i.p.) had no significant effect on the spontaneous activity of LC neurons, but significantly reduced the excitatory response of LC neurons to simple stimuli. Administration of the anxiogenic drug yohimbine (2.0 mg/kg, i.p.) significantly increased the spontaneous activity of LC neurons. These results support the hypothesis that LC neurons play a role in aversive but not appetitive conditioning, and are consistent with the hypothesis that these neurons may play a role in anxiety. These data are discussed within the broader context of LC neurons mediating the organism's adaptive response to environmental or physiological challenges.