The effects of the selective 5-HT2C receptor antagonist SB 242084 on learned helplessness in male Fischer 344 rats

  title={The effects of the selective 5-HT2C receptor antagonist SB 242084 on learned helplessness in male Fischer 344 rats},
  author={Paul V. Strong and Benjamin N. Greenwood and Monika Fleshner},
RationaleRats exposed to an uncontrollable stressor demonstrate a constellation of behaviors such as exaggerated freezing and deficits in shuttle box escape learning. These behaviors in rats have been called learned helplessness and have been argued to model human stress-related mood disorders. Learned helplessness is thought to be caused by hyperactivation of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) and a subsequent exaggerated release of 5-HT in DRN projection sites… 

A double dissociation in the effects of 5-HT2A and 5-HT2C receptors on the acquisition and expression of conditioned defeat in Syrian hamsters.

Results suggest that serotonin acts at separate 5-HT2 receptors to facilitate the acquisition and expression of defeat-induced changes in social behavior.

5-HT2C Receptors in the Basolateral Amygdala and Dorsal Striatum Are a Novel Target for the Anxiolytic and Antidepressant Effects of Exercise

The findings suggest that activation of 5-HT2CR in discrete brain regions contributes to specific anxiety- and depression-like behaviors and may indicate potential brain sites involved in the anxiolytic and antidepressant effects of exercise, and implicates the 5- HT2CR as a target for the beneficial effects of physical activity on mental health.

A role for 5-HT1A receptors in the basolateral amygdala in the development of conditioned defeat in Syrian hamsters

Activation of 5-HT2A receptor disrupts rat maternal behavior

Evaluation of chemically diverse 5-HT2C receptor agonists on behaviours motivated by food and nicotine and on side effect profiles

These studies support the utility of 5-HT2C agonists as a therapeutic approach to treat nicotine dependence and plasma exposure levels after acute lorcaserin treatment suggest that equivalent dosages could be used to evaluate these drugs in obesity and smoking cessation trials.



Freewheel Running Prevents Learned Helplessness/Behavioral Depression: Role of Dorsal Raphe Serotonergic Neurons

It is suggested that freewheel running prevents behavioral depression/LH and attenuates DRN 5-HT neural activity during uncontrollable stress and an increase in5-HT1A inhibitory autoreceptor expression may contribute to the attenuation of DRN 4-HT activity and the prevention of LH in physically active rats.

Antidepressant-like effects of the novel, selective, 5-HT2C receptor agonist WAY-163909 in rodents

The results demonstrate that the novel 5-HT2C receptor agonist WAY-163909 produces rapid onset antidepressant-like effects in animal models and may be a novel treatment for depression.

Influence of the 5-HT2C receptor antagonist, SB-242084, in tests of anxiety

Anxiety-like effects induced by acute fluoxetine, sertraline or m-CPP treatment are reversed by pretreatment with the 5-HT2C receptor antagonist SB-242084 but not the 5-HT1A receptor antagonist WAY-100635.

The results suggest that increased anxiety in rodents, and possibly, also in humans (e.g. agitation or jitteriness after SSRIs and panic after m-CPP), caused by acute administration of SSRI antidepressants or m- CPP, are mediated by activation of 5-HT2C receptors.

Dual role of 5-HT in defense and anxiety

Anxiety-like behaviors produced by acute fluoxetine administration in male Fischer 344 rats are prevented by prior exercise

Results are consistent with the idea that exercise can produce resistance against the anxiogenic effects of acute increases in 5-HT and suggest that acute behavioral effects of antidepressants can depend on history of physical activity.

5-HT2C receptor mediation of unconditioned escape behaviour in the unstable elevated exposed plus maze

The results suggest that the escape-related behaviours exhibited by animals in the UEEPM are mediated, at least in part, by activation of the 5-HT2C receptor subtype.

5-HT2 receptor mechanisms of the dorsal periaqueductal gray in the conditioned and unconditioned fear in rats

The present results suggest that past stressful experience can produce changes in the synaptic function of 5-HT2 receptors within the dPAG with important impact on the expression of defensive behaviors.

Role of 5-HT in stress, anxiety, and depression