Elsevier

Neuroscience

Volume 86, Issue 2, 1 June 1998, Pages 485-497
Neuroscience

5-Hydroxytryptamine-induced excitatory postsynaptic currents in neocortical layer V pyramidal cells: suppression by μ-opiate receptor activation

https://doi.org/10.1016/S0306-4522(98)00043-8Get rights and content
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Abstract

Activation of 5-hydroxytryptamine-2A receptors increases the frequency of excitatory postsynaptic currents through a focal action at apical, but not basilar, dendrites of neocortical layer V pyramidal cells. Since μ-, δ- and κ-opiate receptors are known to inhibit depolarization-induced glutamate release in cerebrocortical slices, we examined the opiate receptor subtype(s) that suppress(es) 5-hydroxytryptamine-induced excitatory postsynaptic currents in the medial prefrontal cortex and whether this suppression was occurring through a presynaptic or a postsynaptic mechanism. Only opioid agonists that act upon μ-receptors (i.e. [d-Ala2,N-Me-Phe4,Gly-ol5]enkephalin, the endogenous μ-selective agonist endomorphin-1 and the non-selective opioid agonist [Met]enkephalin) suppressed 5-hydroxytryptamine-induced excitatory postsynaptic currents. The δ-agonist [d-phen2,5]enkephalin and the κ-agonist U50,488 were ineffective. Only the selective μ-antagonist CTOP blocked the suppressant effect of enkephalin, while the selective δ-antagonist naltrindole and the selective κ-antagonist nor-binaltorphimine were ineffective. Since the 5-hydroxytryptamine-induced excitatory postsynaptic currents are mediated by α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-type excitatory amino acid receptors, the failure of μ-agonists to either block postsynaptic AMPA responses or induce outward currents in layer V pyramidal cells suggest that μ-agonists are acting at a presynaptic site to block 5-hydroxytryptamine-induced excitatory postsynaptic currents. Strikingly, a regional selectivity in the suppressant effect of μ-receptor activation on 5-hydroxytryptamine-induced excitatory postsynaptic currents exists, as 300 nM [d-Ala2,N-Me-Phe4,Gly-ol5]enkephalin suppressed 5-hydroxytryptamine-induced excitatory postsynaptic currents in the medial prefrontal cortex by nearly 100%, while in the frontoparietal cortex 1 μM [d-Ala2,N-Me-Phe4,Gly-ol5]enkephalin suppressed 5-hydroxytryptamine-induced excitatory postsynaptic currents by only 58%.

This is the first demonstration of a previously unsuspected physiological interaction between 5-hydroxytryptamine-2A and μ-opiate receptors and may be relevant to the relationship between these receptors and both mood and psychotic disorders.

Keywords

5-HT2A receptor
5-HT
medial prefrontal cortex
opiates
μ-receptors
endomorphin-1

Abbreviations

ACSF, artificial cerebrospinal fluid
AMPA, α-amino-3-hydroxy-5-methylisoxazole-4-propionate
CTOP, Definition?
DAMGO, [d-Ala2,N-Me-Phe4,Gly-ol5]enkephalin
DPDPE, [d-phen2,5]enkephalin
EPSC, excitatory postsynaptic current
EPSP, excitatory postsynaptic potential
HEPES, N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid
5-HT, 5-hydroxytryptamine
TTX, tetrodotoxin

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