Influence of social isolation in the rat on serotonergic function and memory--relevance to models of schizophrenia and the role of 5-HT₆ receptors.

There is increasing awareness of the importance that early environmental factors have on brain development and their role in the neurobiology of neurodevelopmental disorders including schizophrenia. The isolation reared rat attempts to model adverse effects that human social isolation (absence of social contact) can have on normal brain development. The isolation reared rat also models aspects of schizophrenia including the development of persistent learning and memory deficits. This short review concentrates on the effects of isolation rearing on cognition, including deficits in novel object discrimination, and the neural mechanisms that may underlie this impairment. There is evidence that a key effect of social isolation may be loss of neuronal plasticity combined with change in the functional state of various cortical and hippocampal neurotransmitters, including glutamate and serotonin. Reduced glutamate function may underlie the deficits in novel object discrimination, which can be reversed by administration of a 5-HT(6) receptor antagonist. This suggests that the 5-HT(6) antagonists may act by reducing 5-HT(6) receptor mediated activation of GABA, resulting in glutamate disinhibition. Thus drugs acting at 5-HT(6) receptors may offer a novel approach to treat neurodevelopmental cognitive symptoms, including those seen in schizophrenia.