title: Cardiovascular effects of microinjections of opioid agonists into the 'Depressor Region' of the ventrolateral periaqueductal gray region.
abstract: Microinjections of excitatory amino acids made into the ventrolateral midbrain periaqueductal gray of the rat have revealed that neurons in this region integrate a reaction characterised by quiescence, hyporeactivity, hypotension and bradycardia. Microinjections of both excitatory amino acids and opioids into the ventrolateral periaqueductal gray have shown also that it is a key central site mediating analgesia. The effects of injections of opioids into the ventrolateral periaqueductal gray on arterial pressure and heart rate or behaviour are unknown. In this study we first mapped in the rat the extent of the ventrolateral periaqueductal gray hypotensive region as revealed by microinjections of excitatory amino acids. We found that ventrolateral periaqueductal gray depressor region extended more rostrally than previously thought into the tegmentum ventrolateral to the periaqueductal gray. Subsequently we studied for the first time, the effects of microinjections of mu-, delta-, and kappa-opioid agonists made into the ventrolateral periaqueductal grey depressor region. In contrast to the effects of excitatory amino acid injections, microinjections of the mu-opioid agonist ([D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin) evoked hypertension and tachycardia at approximately 50% of sites. Similar to excitatory amino acid injections, microinjections of both the delta-opioid agonist ([D-Pen2,D-Pen5]enkephalin), and the kappa-opioid agonist ((5,7,8)-(+)-N-Methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-y l]-benzeneacetamide) evoked either a hypotension and bradycardia, or had no effect. These results indicate that different opiate receptor subtypes are present on a distinct population of ventrolateral periaqueductal gray neurons, or at different ventrolateral periaqueductal gray synaptic locations (pre- or post-synaptic).
authors.affiliation: Department of Anatomy and Histology and Institute for Biomedical Research, The University of Sydney, NSW, Australia. keay@anatomy.su.oz.au
authors.forename: K A
authors.initials: KA
authors.lastname: Keay
authors.forename: L J
authors.initials: LJ
authors.lastname: Crowfoot
authors.forename: N S
authors.initials: NS
authors.lastname: Floyd
authors.forename: L A
authors.initials: LA
authors.lastname: Henderson
authors.forename: M J
authors.initials: MJ
authors.lastname: Christie
authors.forename: R
authors.initials: R
authors.lastname: Bandler
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000503:physiopathology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology; D007022:Hypotension / Q000503:physiopathology; D008297:Male; D008845:Microinjections; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D010487:Periaqueductal Gray / Q000737:chemistry / Q000502:physiology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists*; D017465:Receptors, Opioid, delta / Q000819:agonists; D017473:Receptors, Opioid, kappa / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists
chemical_list: D000700:Analgesics; D044482:Benzeneacetamides; D004745:Enkephalins; D018846:Excitatory Amino Acids; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D006710:Homocysteine; C007956:homocysteic acid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; C045444:U 69593