Effects on Depression-Like Behavior

Abstract

Depression is a heterogeneous, multifaceted disorder with symptoms manifested at the psychological, behavioral, and physiological level. This is perhaps why it is so difficult to mimic the disorder in the laboratory (American Psychiatric Association 1994). Many of the human symptoms of depression such as recurring thoughts of death or suicide or having excessive thoughts of guilt as described in the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM IV) are impossible to be modeled in mice or rats. The question, therefore, remains impenetrable as to whether we can ever assume a mouse or rat is “depressed.” Evolutionary theories have been proposed for psychiatric disorders (Jones and Blackshaw 2000; Nesse 2000), which would plausibly predict that also lower animal species can exhibit behaviors useful in modeling human depression. However, such hypotheses are heavily debated and are difficult to address empirically (Dubrovsky 2002; McLoughlin 2002). Another difficulty in assessing depressive states in rodents is that the underlying pathophysiology in depression is still unresolved. Further, the mode of action of clinically effective antidepressants is not yet understood beyond the fact that they primarily alter monoamine neurotransmission (Nestler et al. 2002; Frazer 1997; Richelson 2001; Blier 2001).