Table 3.
Summary of the effects of first-line antidepressants, selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), other monoamine transport inhibitors, norepinephrine reuptake inhibitors (NRI), and nonselective monoamine transporter inhibitors on the expression and function of Cx43.
| Agent (Class) |
Model (Region) | Treatment (Dose, Duration) |
Effect (Function) |
Reference |
|---|---|---|---|---|
| Fluoxetine (SSRI) |
Rat (frontal) | in vivo (20 mg/kg for 21 days) |
Increase (protein) |
[76] |
| rat (frontal) | in vivo (10 mg/kg for 21 days) |
increase (mRNA/protein) (gap junction: no effect) |
[59] | |
| Rat (frontal) chronic unpredictable stress | in vivo (10 mg/kg for 21 days) |
increase (mRNA/protein) (gap junction: augmentation) |
[59] | |
| astrocytoma cells (1321N1/U87MG) |
in vitro (30‒60 µM for 24 h) |
increase (mRNA/protein) | [80] | |
| Mouse (cortical astrocyte) | in vitro (10 µM for 24 h) |
no effect (protein) (gap junction: inhibition) |
[75] | |
| Mouse lipopolysaccharide (cortical astrocyte) |
in vitro (10 µM for 24 h) |
(hemichannel: inhibition) | [75] | |
| mouse exogenous corticosterone (hippocampus) | in vivo (18 mg/kg for 28 days) |
Decreased (phosphorylated protein) |
[64] | |
| Fluvoxamine (SSRI) |
rat (cortical astrocyte) | in vitro (25 µM for 48 h) |
increase (protein) | [77] |
| Paroxetine (SSRI) |
Mouse (cortical astrocyte) |
in vitro (5 µM for 24 h) |
no effect (protein) (gap junction: augmentation) |
[75] |
| Mouse lipopolysaccharide (cortical astrocyte) |
in vitro (5 µM for 24 h) |
(hemichannel: inhibition) | [75] | |
| Reboxetine (NRI) |
Mouse (cortical astrocyte) | in vitro (10 µM for 24 h) |
no effect (protein) (gap junction: no effect) |
[75] |
| mouse lipopolysaccharide (cortical astrocyte) |
in vitro (10 µM for 24 h) |
(hemichannel: inhibition) | [75] | |
| Duloxetine (SNRI) |
Rat (frontal) | in vivo (10 mg/kg for 21 days) |
increase (mRNA/protein) (gap junction: no effect) |
[59] |
| Rat (frontal) chronic unpredictable stress |
in vivo (10 mg/kg for 21 days) |
increase (mRNA/protein) (gap junction: augmentation) |
[59] | |
| mouse (cortical astrocyte) |
in vitro (5 µM for 24 h) |
no effect (protein) (gap junction: no effect) |
[75] | |
| mouse lipopolysaccharide (cortical astrocyte) |
in vitro (5 µM for 24 h) |
(hemichannel: inhibition) | [75] | |
| Venlafaxine (SNRI) |
mouse (cortical astrocyte) |
in vitro (5 µM for 24 h) |
no effect (protein) (gap junction: inhibition) |
[75] |
| mouse lipopolysaccharide (cortical astrocyte) |
in vitro (5 µM for 24 h) |
(hemichannel: inhibition) | [75] | |
| Milnacipran (SNRI) |
rat cortical astrocyte | in vitro (25 µM for 48 h) |
no effect (protein) | [77] |
| Cocaine | rat cortical astrocyte | in vitro (100 µM for 48 h) |
no effect (protein) | [77] |
| (nonselective monoamine transporter inhibitor) | ||||
We searched MEDLINE using the keywords “(((connexin) OR (hemichannel) OR (gap junction)) AND ((antidepressant) OR (psychotropic drugs)))” for papers published by 1 November 2020. Relevant articles were obtained in full and assessed for inclusion independently by reviewers. Disagreements among reviewers were resolved via discussion to reach a consensus.