1.Opioid actions on rat anterior cingulate cortex neurons in vitro.
Tanaka E;North RA J Neurosci. 1994 Mar;14(3 Pt 1):1106-13.
Intracellular recordings were made from layer V pyramidal neurons in slices of rat anterior cingulate cortex, using electrodes that contained potassium methylsulfate and biocytin. [Met5]enkephalin (300 nM to 30 microM) reversibly reduced the amplitude of EPSPs evoked by stimulation of the subcortical white matter; the half-maximal concentration was about 800 nM. These EPSPs were blocked by (+/-)-2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione. [Met5]enkephalin also reduced the amplitude of bicuculline-sensitive IPSPs evoked by stimulation within layer V; the half-maximal concentration was about 60 nM. Both these actions of [Met5]enkephalin were mimicked by the delta-selective agonist DPDPE (Tyr-D-Pen-Gly-Phe-D-Pen) but not by the mu-selective agonist DAMGO (Tyr-D-Ala-Gly-MePhe-Gly-ol); they were blocked by the delta-selective antagonist naltrindole (apparent dissociation constant of about 0.3 nM) but not by the mu-selective antagonist CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2). [Met5]enkephalin did not change the amplitudes of depolarizations evoked by direct application of glutamate or hyperpolarizations evoked by direct application of muscimol (at -55 mV).
2.Electrophysiological demonstration of mu, delta and kappa opioid receptors in the ventral pallidum.
Mitrovic I;Napier TC J Pharmacol Exp Ther. 1995 Mar;272(3):1260-70.
Opioid mu, kappa and delta receptors are present in significant densities in the ventral pallidum (VP). To examine their contribution to VP neuronal activity, changes in firing rate during microiontophoresis of the receptor-selective agonists [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO) (mu), [D-Pen2,5]-enkephalin (DPDPE) (delta) and trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cy-clohexyl]-benzene-acetamide methane sulfonate (U50488H) (kappa), and the antagonists D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) (mu) and norbinaltorphimine (kappa) were determined in chloral hydrate-anesthetized rats. A majority of the neurons demonstrated ejection current-dependent decreases in neuronal activity to DAMGO and U50488H. The rate suppressions were attenuated by coiontophoresis of the homotypic antagonist, indicating receptor subtype-specificity of the responses. In contrast, DPDPE decreased firing in only 24% of the recorded neurons. In those neurons tested with all three agonists, nearly 70% were sensitive to at least one. Among responding neurons, approximately one-quarter was influenced by activation of all three receptor subtypes while another quarter was sensitive to only mu activation.
3.Spinal GABA receptors mediate brain delta opioid analgesia in Swiss Webster mice.
Rady JJ;Fujimoto JM Pharmacol Biochem Behav. 1995 Aug;51(4):655-9.
Morphine and heroin act on supraspinal mu-opioid receptors in ICR mice to activate descending noradrenergic and serotonergic systems to inhibit the tail flick response. Antinociception induced by supraspinal [D-Pen2,5]-enkephalin (DPDPE, delta agonist) involves a descending system mediated by spinal gamma-aminobutyric acid, GABAA and GABAB, receptors. Because in Swiss Webster mice the receptor selectivity of heroin changes to delta whereas morphine remains mu, the purpose of the present study was to determine whether this delta action of heroin was mediated spinally by GABAA and GABAB receptors. Bicuculline (GABAA receptor antagonist) and picrotoxin (chloride ion channel blocker) given intrathecally produced rightward shifts in the dose-response curves of DPDPE and heroin given intracerebroventricularly. Thus, spinal GABAA receptors were involved. Intrathecal administration of 2-hydroxysaclofen (GABAB receptor antagonist) also shifted the dose-response curves to the right. Thus, the antinociception produced by heroin, like DPDPE, by activation of delta receptors in the brain of Swiss Webster mice involved both GABAA and the GABAB receptors in the spinal cord.
