dextromethorphan and dermorphin

1. The effects of various opioid receptor agonists given directly by means of a chronically implanted cannula into the locus coeruleus (LC) on behaviour and ECoG activity, continuously analysed, and quantified as total power spectrum (0-16 Hz) and in preselected frequency bands (0-3; 3-6; 6-9; 9-12 and 12-16 Hz), were studied in rats. 2. Dermorphin (0.05, 0.5, 1, 2 and 5 pmol) and Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (DAMGO; 1, 10, 30, 100 pmol and 1 nmol), two typical mu-receptor agonists, applied unilaterally or bilaterally directly into the LC, produced a typical dose-dependent ECoG synchronization with a significant increase in total power spectrum as well as in the lower frequency bands. Dermorphin was found to be approximately 30 times more powerful than DAMGO in producing similar quantitative ECoG changes. 3. D-Ala-D-Leu-Thr-Gly-Gly-Phe-Leu (DADLE; 1, 10, 50 and 100 pmol), a selective delta-receptor agonist, micro-infused into the LC produced dose-dependent behavioural soporific effects and ECoG increase in total power spectrum as well as in 3-6, 6-9, 9-12 Hz frequency bands. In comparison to dermorphin, the ECoG power spectrum effects of DADLE were 10 fold less potent, whereas in comparison to DAMGO it was approximately 3 times more potent. A lower dose (0.1 pmol) was ineffective in changing behaviour and ECoG power spectrum. 4. The microinfusion into the LC of U 50, 488H, a selective Kappa-opioid receptor agonist, (0.25, 1, 2.5, 5 and lOpmol) produced a typical pattern characterized by a first short-lasting (3-25 min) phase of behavioural arousal and ECoG desynchronization, followed by a longer lasting (20-130min according to the dose) phase of behavioural sleep and ECoG synchronization. A lower dose (0.1 pmol) was ineffective in changing behaviour and ECoG power spectrum. 5. Dextromethorphan and ketamine, two selective agonists at sigma-receptors given into the LC (1, 5 and 1Opmol) induce behavioural arousal, increase in locomotor activity and an intense pattern of stereotypedm movements. However, by increasing the dose of ketamine (50 and lOOpmol), marked sedation, postural changes and an increase in low frequency ECoG bands, sometimes associated with high amplitude fast frequency potentials, were observed. 6. Naloxone applied directly into the LC (1 and 2 pmol 15min before) was able to prevent the behavioural and ECoG effects induced by dermorphin, DAMGO and DADLE. Higher doses of naloxone (1Opmol into the LC) were however, required to antagonize the

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Amino Acid Sequence; Animals; Dextromethorphan; Electroencephalography; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine-2-Alanine; Enkephalins; Ketamine; Locus Coeruleus; Male; Molecular Sequence Data; Naloxone; Oligopeptides; Opioid Peptides; Pyrrolidines; Rats; Rats, Inbred Strains; Receptors, Opioid