Hey guys!  We have recently been discussing big current topics in neuropsychology, and the one that caught my interest pertains to the usefulness of animal models.  The “Guinea Pig” has served as a common staple in many experimental sciences for so long that the term has become a cultural cliche.  One must not question their general usefulness. Biologists can identify specific proteins in animals that are analogous to many receptors, immune system components, and neurotransmitters found in the human body.  Thus chemical manipulations can be very informative concerning the effects of drugs on behavior.  However, the chasm of the human mind expands so far and so intricately that the causes of many widespread psychopathologies such as posttraumatic stress disorder and depression remain nebulous.  In studying these afflictions, researchers require not only knowledge of protein function but also that of the entire systems that incorporate them; one must then wonder if the researchers could ever actually induce psychopathology in animals in a way that provides a true representation of the intended human analogs.  If you deprive a rat of sleep for prolonged periods of time or shock it ruthlessly until it learns helplessness, and it demonstrates symptoms of depression such as anhedonia, can we really say that it is depressed like a human, and can this model help us actually find a human treatment? And, more importantly, should such research be utilized in widespread pharmaceutical treatment of more common pathologies?

Decades ago, Elizabeth Gaylord (1977) provided evidence that it might.  In this experiment, she targeted norepinephrine and serotonin as the devious neurotransmitter culprits responsible of causing depression when their stores are depleted.  In her intro, she takes credit for developing many animal models of psychopathology.  In order to construct these animal models, she first had to ask herself what she even considered to be “normal” human depression.  Ultimately she decided to include symptoms resembling anergy, passivity, feelings of helplessness, and a shift in affect towards negativity.  Gaylord believed that depression of this sort might be explained by a faulty function of the monoamine system; thus, she sought to synthesize this condition by injecting rat subjects with different drugs that cause damage to or inhibit serotonin and norepinephrine.  She found that a chemically induced imbalance that favors high norepinephrine levels to lower serotonin levels, the result was a tone of hyper-anxiety.  These subjects demonstrated a high level of energy in their own environments, exploring, approaching humans, and exercising voluntarily.  However, in a novel environment, they quickly became frightened and paranoid, refusing to explore and increasing rearing (vigilant) behaviors.  Furthermore, they demonstrated an increased tendency to hug walls and hide under rocks.  In a stark contrast, the high serotonin group demonstrated a “fearless and nonvigilant” demeanor in a novel environment, as they refused to hide and wandered the field voluntarily.  Interestingly enough, in their own environment, these rats were withdrawn and did not seem to have any motivation, mostly remaining inactive.  This provides strong evidence that norepinephrine and serotonin both play a critical role in the modulation of mood; however, neither of the expressed phenotypes resembled true human depression, which often appears as a combination of the symptoms she found in both imbalances.  Furthermore, in the context of the pharmaceutical question, these results present problems.

Today, the most common manifestations of pharaceutical antidepressents are selective serotonin uptake inhibitors better known and Lexapro, Zoloft, Paxil, and others.  These operate by forcing serotonin, when released, to reside in the synapse longer, effectively increasing its function.  To this day, the exact nature of the mechanisms being modulated by serotonin in this process are not understood.  Ironically, Gaylord’s findings indicate that high serotonin function actually facilitates depressive symptoms.  I will concede that this work is quite old, and research in serotonin research has likely come a long way; I do not attempt to make you believe that system is as reductionist as I have described it, but Gaylord’s work still illustrates how research in psychopharmacology is often conflicting and frustrating.

One of the biggest problems in depression is the fact that depression itself and loneliness not only go hand in hand, but they also perpetuate each other in a cyclical fashion.  Withdrawal from society is the symptom and the problem itself.  Furthermore, in another component of Gaylord’s work, she suggests that imbalances of both serotonin and norepinephrine were both effectively treated with simple social interaction.  This concept is now a component of the widely accepted environmental enrichment theory, which asserts the existence of many quantifiable physical and psychological benefits can be found in a life filled with stimulation from good nutrition, social interaction, and exercise.  Right now, Americans turn to pharmaceutical companies to give them a pill to “make it all better.”  Perhaps many of these people should not be quite so hasty to ingest psycho-modulatory drugs supported by disputed research and instead should first focus on what they have the power to do to help themselves to break the cycle of loneliness and depression.  As Outkast would say, you just gotta get up, get out, and get something…

P.S.  I also just want to make it clear that I am aware of research that supports the miraculous ability of SSRI’s to reverse depressive symptoms in some people.  But, this group is relatively small and may have specific biological factors that predispose them to severe and unprovoked episodes of depression.  Therefore, I assert that antidepressants should not be pursued as a “wonder drug” for the masses.  I strongly believe that most people have the ability to take it into their own hands to improve their situation.  Essentially, they should go out, talk to people, and do the things that stimulate and challenge them on physical and psychological levels.