Reduced attention in mice overproducing corticotropin-releasing hormone

Data from several studies suggest that unrestrained secretion of corticotropin-releasing hormone in the CNS produces several signs and symptoms of depression. Recent evidence indicates that blockade of the CRH receptor 1 reduced depression scores in depressed patients. One of the symptoms that occur is depression is impairment in attentional processes. Whether these impairments are due to alterations in the CRH system are so far unknown. In order to investigate whether overproduction of CRH alters attentional process, transgenic mice overproducing CRH were tested on an operant five choice serial reaction time task, a task which taxes sustained and divided attention. Mutants showed impaired autoshaping. During initial discrimination learning, transgenics performed below wildtype level, but with extended training with long stimulus durations, transgenic animals reached similar accuracy levels as wildtype mice. When animals were tested at shortest stimulus duration (0.5s), a mild but significant impairment in accurate responding emerged in transgenics. This was accompanied by longer correct response latencies, while incorrect latencies did not differ between groups, suggesting attentional impairment in CRH transgenics. Because these animals have been reported to also show increased anxiety-related behaviour, animals were treated with the anxiolytic benzodiazepine diazepam. Diazepam failed to affect accuracy, but transgenic mice showed a stronger behavioural disinhibition. This suggests that the attentional impairment seen in CRH overexpressors is independent of alterations in anxiety-like behaviour. These findings may have implications for understanding the pathophysiology of psychiatric disorders such as depression, where it has been suggested that an overactivity of the CRH system accounts for a variety of symptoms, including hyper-arousal and attentional impairment.