Psychiatry Investig.  2016 Jul;13(4):434-439. 10.4306/pi.2016.13.4.434.

Predictive Validity of Some Common Animal Models of Bipolar Disorder Using Lithium and Lamotrigine Therapy: An Attempt towards a Battery-Based Approach for the Evaluation of Mood Stabilizers

• Kumar M
• Tripathi C
• Verma V
• Padhy BM
• Meshram GG
• Abhilash B

• KMID: 2344742
• DOI: http://doi.org/10.4306/pi.2016.13.4.434

Abstract

OBJECTIVE
To determine the predictive validity of some of the commonly employed models of mania and depression using standard drugs i.e. lithium (70 mg/kg) and lamotrigine (5 mg/kg) in male Wistar rats.
METHODS
The depression facet of bipolar disorder was evaluated using forced swim test, tail suspension test, and chronic mild stress test. The models used to evaluate the mania facet of bipolar disorder were isolation-induced aggression test, saccharine preference test, and morphine-sensitized hyperlocomotion test.
RESULTS
The immobility time was significantly (p<0.05) reduced by lamotrigine in the tail suspension test and the forced swim test, while lithium caused significant (p<0.05) reduction only in the tail suspension test. Rats exposed to chronic mild stress showed the maximal increment of 1% sucrose consumption at the 3rd week of treatment in both the lithium (p<0.001) and lamotrigine (p<0.01) groups. In the isolation-induced aggression test, the aggressive behaviour of rats was significantly reduced by both lithium [approach (p<0.001), attack (p<0.01), and bite (p<0.01)] and lamotrigine [approach (p<0.001), and attack (p<0.05)]. Neither of the drugs were effective in the saccharine preference test. Only lithium was able to significantly (p<0.05) reduce the crossing parameter in morphine-sensitized rats.
CONCLUSION
Our study identifies the chronic mild stress test and isolation-induced aggression test of having the highest predictive validity in the depression and mania facets of bipolar disorder, respectively, and should be a part of a battery of tests used to evaluate novel mood stabilizers.

Keyword

Bipolar disorder; Lithium; Lamotrigine; Predictive validity; Battery-based approach

MeSH Terms

Aggression
Animals*
Bipolar Disorder*
Depression
Exercise Test
Hindlimb Suspension
Humans
Lithium*
Male
Models, Animal*
Rats
Rats, Wistar
Saccharin
Sucrose
Lithium
Saccharin
Sucrose