Behavioural Neuroscience Poster Session
Systemic lupus erythematosus (SLE) is an autoimmune disease which affects multiple organ systems. Various psychiatric symptoms have also been observed in SLE, and among them, depression is most commonly reported 1. One of the core symptoms for the diagnosis of depression is loss of interest or pleasure (anhedonia)2.
MRL/lpr mice spontaneously develop a lupus-like autoimmune disease and the recent finding that these animals show a reduced preference for sucrose suggests a diminished sensitivity to reward or anhedonia3. However, the finding of reduced preference is not sufficient to indicate anhedonia. It is possible that one of the consequences of autoimmune disease is an inability to taste properly. Thus, it may be the case that MRL/lpr mice simply can't taste sucrose. Unlike sucrose, the rewarding effects of amphetamine do not depend on the activation of any particular sensory receptors. Therefore, the present study investigated in MRL/lpr mice the reward value of amphetamine. A conditioned place preference (CPP) paradigm was employed because it does not depend on motor performance to obtain the rewarding effects of the drug. According to the anhedonia hypothesis, it was expected that MRL-lpr mice would not show CPP.
Materials and Methods
The CPP test measures the capacity of a rewarding stimulus to elicit approach responses towards it and maintenance of contact with it4. Since the rewarding effects of a drug are internal, and since it is not possible to direct approach responses towards internal, physiological states, CPP employs the phenomenon of secondary conditioning4. That is, a reward and its presumed internal effect are paired with the external stimuli of a distinctive environment. If, after repeated pairings, the animal increases the time that it spends approaching and maintaining contact with the reward-associated environment, a conditioned place preference is said to have occurred and is attributed to the rewarding properties of the drug.
Ten week old MRL/lpr mice (n=19) and their age-matched congenic controls (MRL +/+; n=16) were habituated to the CPP apparatus for 15 minute periods on 3 consecutive days. Their baseline preference for the two distinctive compartments of the apparatus was determined on the third day. After habituation, four pairing sessions were administered in which mice were injected (i.p.) with amphetamine (0.5 or 1.5 mg/kg) on odd-numbered days and confined to their less preferred compartment for 30 minutes. On even-numbered days, the animals were injected with an equal volume of saline and confined to their more preferred compartment for 30 minutes. On the test day, mice had unrestricted access to both compartments of the CPP apparatus and the time spent in each of the compartments was measured.
After conditioning, both MRL-lpr and MRL-+/+ mice showed a significant increase (p < 0.05) in the time spent on the initially less preferred side, for each dose of amphetamine. These increases were similar in the two substrains (p > 0.05).
Fig 1. CPP to amphetamine in MRL mice.
Discussion and Conclusion
Based on previous findings, it was hypothesized that MRL-lpr mice would not show a conditioned place preference to amphetamine. However, the results of this study indicate not only that MRL-lpr mice show a significant conditioned place preference, but also that they do not differ from control animals in the extent of conditioning, for both doses of amphetamine. Thus, it appears that at the given doses of amphetamine, MRL-lpr mice do not exhibit anhedonia. Accordingly, the finding of blunted sucrose intake could be due to a sensory impairment in MRL-lpr mice. Nevertheless, the present experiment does not necessarily exclude the anhedonia hypothesis, since it is possible that the reward system of MRL-lpr mice is altered to some types of rewards but not others. These ideas will be investigated in further studies.
In addition to a possible anhedonia, MRL-lpr mice show other behavioural symptoms characteristic of depression5. Consequently, they may be a good animal model to study possible immune mechanisms for different symptoms of depression.
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|Prasad, N.; Szechtman, H.; (1998). Anhedonia In Autoimmune MRL Mice: An Evaluation Using The Conditioned Place Preference Paradigm. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Available at URL http://www.mcmaster.ca/inabis98/behavneuro/prasad0447/index.html|
|© 1998 Author(s) Hold Copyright|