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Re: 'safer' not 'better'?

Posted by linkadge on May 14, 2020, at 9:38:51

In reply to Re: 'safer' not 'better'? SLS, posted by undopaminergic on May 14, 2020, at 2:50:02

>The part about hyperexcitable dopamine neurons in >depression sounds confusing and hard to believe, >because dopaminergic stimulants *ameliorate* >depression and they *boost* the effects of VTA >activity in the nucleus accumbens, and they helps >against apathy.

I have read that the firing patterns are important to the antidepressant effects of certain compounds. I.e. a lack of 'burst firing' being associated with depression. It may be dependant on the type of depression. In some instancess 5-ht2c antagonists (which increase burst firing) are antidepressant. In other cases 5-ht2c agonists are antidepressant (and anti-OCD). Likewise, some depression is associated with prefrontal dopamine hyperfunction and some with hypofunction.

Overactivation of the reward system can paradoxically produce depression. In mouse models, chronic stress is associated with a loss of inhibitory GABAergic function in the NAc. Restoring this inhibition of dopamine can reduce depression. It could be that in response to the pain of stress, the brain tries to offset this with increased reward.

I've been through many stressful times where I get reward from the thoughts associated with 'getting through the stress'. I.e. "things are going to be so much better once this is over". However, often when the stress is over, there is, in fact, no reward. The reward system is just activating to get me through a difficult time. One it's over it comes back down and tires to recalibrate towards new goals or rewards.




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