Lateralization of the 5-HT1A receptors in the basolateral amygdala in metabolic and anxiety responses to chronic restraint stress

Behavioral and functional studies describe hemispheric asymmetry in anxiety and metabolic behaviors in responses to stress. However, no study has reported serotonergic receptor (the 5-HT_1A receptor) lateralization in the basolateral amygdala (BLA) in vivo on anxiety and metabolic behaviors under stress. In the present study, the effect of unilateral and bilateral suppression of the 5-HT_1A receptor in the BLA on anxiety, and metabolic responses to chronic restraint stress was assessed. Male Wistar rats 7 days after cannulation into the BLA received chronic restraint stress for 14 consecutive days. 20 minutes before induction of stress, WAY-100–635 (selective 5-HT_1A antagonist) or sterile saline (vehicle) was administered either uni- or bi-laterally into the BLA. Behavioral (elevated plus maze; EPM, and open field test), and metabolic parameter studies were performed. Results showed that stress causes a significant increase in weight gain compared to control. In the non-stress condition, the left and bilaterally, and in the stress condition the right, left, and both sides, inhibition of 5-HT_1A in the BLA reduced weight gain. In the restraint stress condition, only inhibition of the 5-HT_1A receptor in the left BLA led to decreased food intake compared to the control group. In stress conditions, inhibition of the 5-HT_1A receptor on the right, left, and bilateral BLA increased water intake compared to the stress group. Inhibition of the 5-HT_1A receptor on the left side of the BLA by WAY-100–635 induced anxiety-like behaviors in stressed rats. Similarly, WAY-100–635 on the left BLA effectively caused anxiety-like behaviors in both EPM and open field tests in the control animals. In conclusion, it seems that 5-HT_1A receptors in the left BLA are more responsible for anxiety-like behaviors and metabolic changes in responses to stress.