MORPHOMETRIC EVIDENCE FOR LITHIUM

Gwendolyn

Chronic

exposure to restraint stress, psychosocial stress, and systemic or oral

administration of the stress-hormone corticosterone (CORT) induces a

morphological reorganization in the hippocampus of rats, in which adrenal

steroids and excitatory amino acids mediate a reversible remodeling of apical

dendritic branch points and length on pyramidal cell neurons in the CA3 region

of the hippocampus (Wantanabe et al., 1992; Magarinos et al, 1995; Magarinos et

al, 1999; Conrad et al, 1999).  This stress-induced “neuronal remodeling” can be

prevented with treatment with selective antidepressants and anticonvulsive drugs

(Magarinos et al., 1999).  Lithium is commonly prescribed to patients with mood

disorders (Bowden 1996), and it is reported to regulate aspects of neuronal

signal transduction, such as the G-protein-coupled cyclic AMP (cAMP) pathway and

polyphosphoinositide generated second messengers.  Lithium treatment has been

implicated in changes in glutamate activity, and shown to prevent glutamate

toxicity in cultured neurons (Nonaka, et al., 1998). Given previous reports of

opposing effects of chronic restraint stress versus lithium treatment, we

examined the effects of chronic lithium treatment on neuronal architecture of

the CA3 regions of the hippocampus.  Our results indicate that chronic stress

results in a decrease of dendritic length and branch points on pyramidal cell

neurons in the CA3 subregion, and that these effects can be prevented with