The sedating antidepressant trazodone impairs sleep-dependent cortical plasticity.
BACKGROUND
Recent findings indicate that certain classes of hypnotics that target GABA(A) receptors impair sleep-dependent brain plasticity. However, the effects of hypnotics acting at monoamine receptors (e.g., the antidepressant trazodone) on this process are unknown. We therefore assessed the effects of commonly-prescribed medications for the treatment of insomnia (trazodone and the non-benzodiazepine GABA(A) receptor agonists zaleplon and eszopiclone) in a canonical model of sleep-dependent, in vivo synaptic plasticity in the primary visual cortex (V1) known as ocular dominance plasticity.


RESULTS
After a 6-h baseline period of sleep/wake polysomnographic recording, cats underwent 6 h of continuous waking combined with monocular deprivation (MD) to trigger synaptic remodeling. Cats subsequently received an i.p. injection of either vehicle, trazodone (10 mg/kg), zaleplon (10 mg/kg), or eszopiclone (1-10 mg/kg), and were allowed an 8-h period of post-MD sleep before ocular dominance plasticity was assessed. We found that while zaleplon and eszopiclone had profound effects on sleeping cortical electroencephalographic (EEG) activity, only trazodone (which did not alter EEG activity) significantly impaired sleep-dependent consolidation of ocular dominance plasticity. This was associated with deficits in both the normal depression of V1 neuronal responses to deprived-eye stimulation, and potentiation of responses to non-deprived eye stimulation, which accompany ocular dominance plasticity.


CONCLUSIONS
Taken together, our data suggest that the monoamine receptors targeted by trazodone play an important role in sleep-dependent consolidation of synaptic plasticity. They also demonstrate that changes in sleep architecture are not necessarily reliable predictors of how hypnotics affect sleep-dependent neural functions.
Aton
Sara J
SJ
Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Seibt
Julie
J
Dumoulin
Michelle C
MC
Coleman
Tammi
T
Shiraishi
Mia
M
Frank
Marcos G
MG
D000704:Analysis of Variance; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D002415:Cats; D004569:Electroencephalography; D009473:Neuronal Plasticity / Q000187:drug effects*; D012890:Sleep / Q000502:physiology*; D014196:Trazodone / Q000494:pharmacology*; D014793:Visual Cortex / Q000187:drug effects* / Q000502:physiology
D018687:Antidepressive Agents, Second-Generation; D014196:Trazodone