Role of central mu, delta-1, and kappa-1 opioid receptors in opioid-induced muscle rigidity in the rat.

BACKGROUND: Opioids appear to produce their physiologic effects by binding to at least three types of opioid receptors, the mu (mu), delta (delta), and kappa (kappa) receptors. Muscle rigidity occurs after administration of supra-analgesic doses of potent mu-preferring agonists like alfentanil. The role of different supraspinal opioid receptors in this rigidity has been addressed only recently. To elucidate the contribution of central mu, delta, and kappa receptors to muscle rigidity, the effects of intracerebroventricularly administered opioid receptor-selective agonists and antagonists on alfentanil-induced muscle rigidity were examined in rats. METHODS: Rats in which chronic intracerebroventricular cannulae had been implanted received an intracerebroventricular infusion of either saline or a mu (D-Ala2,N-Me-Phe4-Gly5-olenkephalin; DAMGO), delta(1) (D-Pen2,D-Pen5-enkephalin; DPDPE), or kappa(1) (trans-(+/-)-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl)- cyclohexyl)-benzene-acetamide methane sulfonate; U50,488H) opioid agonist. Ten minutes later, they received either saline or the mu-agonist alfentanil subcutaneously. Muscle rigidity was assessed using hindlimb electromyographic activity. Different groups of animals were pretreated with an intracerebroventricular infusion of either saline or a mu (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2; CTAP), delta (naltrindole), or kappa(1) (norbinaltorphimine) opioid antagonist before administration of either saline or a selective intracerebroventricular agonist. RESULTS: The mu agonist DAMGO alone dose-dependently induced muscle rigidity. This effect was antagonized by pretreatment with the mu-selective antagonist CTAP. Neither DPDPE nor U50,488H, when administered alone, affected muscle tone. However, both the delta(1) and kappa(1) agonists dose-dependently attenuated alfentanil-induced rigidity. This antagonism of alfentanil rigidity was abolished after pretreatment with the delta (naltrindole) and kappa(1) (nor-binaltorphimine) antagonists, respectively. CONCLUSIONS: The present data demonstrate that whereas systemic opiate-induced muscle rigidity is primarily due to the activation of central mu receptors, supraspinal delta(1) and kappa(1) receptors may attenuate this effect. This finding is consistent with previous demonstrations of functional interactions between different central opioid receptor populations in other opiate effects, and could have important pharmacotherapeutic implications.

Cholecystokinin-like immunoreactivity in cat inferior colliculus. Light and ultrastructural study.

Cholecystokinin-like immunoreactive (CCK-LI) neurons are observed in the pericentral nucleus, the external nucleus and the dorsomedial part of the central nucleus of the cat's inferior colliculus. The largest number of CCK-LI cell bodies is observed in the caudal part of the pericentral nucleus. Using the electronmicroscopical examination we distinguish two different types of CCK-LI neurons. The first type CCK-LI neurons is characterized by a relatively large nucleus, surrounded by a dark rim of cytoplasm containing single cisterns of granular endoplasmic reticulum, few mitochondria and lysosomes. The second type CCK-LI neurons are smaller than the neurons of the first type. The nucleus is relatively larger while the cytoplasmic rim is quite thin. The CCK-LI immunoreactivity is also found in the large, medium-sized and small dendrites as well as in the dendritic spines. The CCK-LI axon terminals contain small round or pleomorphic vesicles. Sometimes they show a mixed population of clear and dense core vesicles. The immunoreactive terminal boutons establish typical asymmetrical synaptic contacts with dendritic spines, small or medium-sized dendrites. More rarely, the immunoreactive axon terminals perform symmetrical or intermediate synaptic contacts with proximal dendritic trunks or perikarya.

Neurotensin immunoreactivity in the colliculus inferior of cat: light and electron microscopic investigations.

Neuronal perikarya with neurotensin-like immunoreactivity (NT-LI) are found in the pericentral and external nuclei and the dorsomedial part of the central nucleus of the inferior colliculus. On electron-microscopic examination, these neurons are characterized by a relatively large nucleus, a small amount of cytoplasm and paucity of organelles. NT-LI is observed in large and small dendrites and dendritic spines as well as in axon terminals which contain small round or elongated clear vesicles and/or dense core vesicles. The immunoreactive terminal boutons make asymmetrical axodendritic and symmetrical axo-somatic synapses mainly on non-immunoreactive elements.