Dopamine and serotonin inversely modulate D2 medium spiny neurons to regulate cocaine reward - PubMed
3 hours ago
- #neuroscience
- #serotonin
- #dopamine
- Dopamine (DA) and serotonin (5HT) have opposing roles in the striatum, with DA promoting approach behaviors and 5HT promoting patience or avoidance.
- 5HT receptors, particularly Gq-coupled 5HT2a and 5HT2c receptors, are enriched on D2 medium spiny neurons (D2-MSNs) and have excitatory effects on these neurons.
- DA and 5HT inversely regulate the firing activity of D2-MSNs, with 5HT's excitatory effect being blocked by 5HT2a and 5HT2c receptor antagonists.
- Increasing striatal 5HT release preferentially activates D2-MSNs, as shown by cfos expression, confirming the in vivo relevance of 5HT's excitatory effect.
- Loss of 5HT2c receptor function in D2-MSNs, but not D1-MSNs, increases sensitivity to cocaine's behavioral effects, indicating that 5HTergic excitation of D2-MSNs counteracts DA's reinforcing effects.
- The study identifies a key circuit mechanism where DA and 5HT oppositely modulate D2-MSN activity to regulate cocaine reward, supporting classic theories of their antagonistic roles.