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Opioid actions on neurons of rat lateral amygdala in vitro
Abstract:
Intracellular recordings were made from neurons in the lateral nucleus of the amygdala, in a slice of rat brain that was superfused in vitro. [Met5]enkephalin (3-30 microM) and the mu receptor selective agonist DAMGO (Tyr-D-Ala-Gly-MePhe-Gly-ol; 0.3-3 microM) hyperpolarized about 50% of cells; this was blocked by naloxone and by the mu receptor antagonist CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2). The pA2s for naloxone and CTOP were 8.3 and 7.7, respectively. DPDPE (Tyr-D-Pen-Gly-Phe-D-Pen: delta receptor selective) and U50488 (trans-(+-)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide methane sulfonate; kappa receptor selective) had no effect. Synaptic potentials mediated by gamma-aminobutyric acid (GABA) acting at GABAA receptors were elicited by focal stimulation of the slice in a combination of 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (10 microM) and 4-aminophosphonovaleric acid (30 microM). They were inhibited by up to 60% by DAMGO and by DPDPE. The action of DAMGO was blocked by CTOP but not by the delta-selective antagonist ICI174864 (N,N-bisallyl-Tyr-Aib-Aib-Phe-Leu-OH, Aib = aminoisobutyrate). The action of DPDPE was blocked by ICI174864 but not by CTOP. Depolarizations elicited by addition of GABA to the superfusing solution were not affected by opioids. It is concluded that activation of mu opioid receptors hyperpolarizes about 50% of lateral amygdala neurons. Activation of either mu or delta receptors also inhibits presynaptically the release of GABA.
Insights
Opioid receptors in the amygdala influence neuronal activity. Mu opioid receptor activation hyperpolarizes lateral amygdala neurons, while mu and delta receptor activation inhibit GABA release.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- The lateral nucleus of the amygdala plays a crucial role in emotional processing.
- Opioid receptors are implicated in modulating neuronal excitability and synaptic transmission.
Purpose of the Study:
- To investigate the effects of specific opioid receptor agonists and antagonists on neurons in the lateral nucleus of the amygdala.
- To determine the involvement of mu and delta opioid receptors in regulating GABAergic synaptic transmission in this brain region.
Main Methods:
- Intracellular recordings from rat lateral amygdala neurons in vitro.
- Application of selective mu ([Met5]enkephalin, DAMGO), delta (DPDPE), and kappa (U50488) opioid receptor agonists.
- Use of opioid receptor antagonists (naloxone, CTOP, ICI174864) to block receptor activation.
- Electrically evoked GABAergic synaptic potentials were measured.
Main Results:
- Activation of mu opioid receptors ([Met5]enkephalin, DAMGO) hyperpolarized approximately 50% of lateral amygdala neurons, an effect blocked by naloxone and CTOP.
- Neither delta (DPDPE) nor kappa (U50488) receptor agonists affected neuronal membrane potential.
- Both DAMGO (mu) and DPDPE (delta) inhibited evoked GABA release presynaptically, with distinct antagonist profiles.
- Direct application of GABA did not alter neuronal responses to opioids.
Conclusions:
- Mu opioid receptor activation directly hyperpolarizes a subpopulation of lateral amygdala neurons.
- Both mu and delta opioid receptors presynaptically inhibit GABA release in the lateral amygdala.
- These findings highlight the complex role of opioid signaling in modulating amygdala function.