Biomaterial Database

Drug dependent sex-differences in periaqueducatal gray mediated antinociception in the rat. 2009

Erin N Bobeck, and Amy L McNeal, and Michael M Morgan

Department of Psychology, Washington State University, Vancouver, WA 98686, USA. erin.bobeck@email.wsu.edu

Mu-opioid receptor (MOPr) agonists, such as morphine, produce greater antinociception in male compared to female rats. The ventolateral periaqueductal gray (vlPAG) appears to contribute to this sex-difference despite fewer vlPAG output neurons projecting to the rostral ventromedial medulla in male compared to female rats. This greater projection in female rats suggests that non-opioid activation of vlPAG output neurons should produce greater antinociception in female compared to male rats. This hypothesis was tested by comparing the time course and antinociceptive potency of microinjecting MOPr agonists (morphine, DAMGO, fentanyl) and non-opioid compounds (bicuculline, kainic acid) into the vlPAG of female and male rats. Microinjection of morphine or DAMGO produced antinociception that had a slow onset (peak from 15 to 30min) and long duration (60min) compared to the antinociception produced following microinjection of fentanyl, bicuculline, or kainic acid (peak effect at 3min; duration less than 30min). No sex-differences in the time courses were evident. All five compounds caused a dose-dependent antinociception when microinjected into the vlPAG. Antinociceptive potency was significantly greater in male compared to female rats following microinjection of morphine, DAMGO, and bicuculline, but not following microinjection of fentanyl or kainic acid. In no case did activation of the vlPAG produce greater antinocicepiton in female compared to male rats. These findings demonstrate that the vlPAG can produce comparable antinociception in female and male rats, but antinociception produced by inhibition of GABAergic neurons (whether by morphine or the GABA(A) receptor antagonist bicuculline) produces greater antinociception in males.

UI	MeSH Term	Description	Entries
D007608	Kainic Acid	(2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose.	Digenic Acid,Kainate,Acid, Digenic,Acid, Kainic
D008297	Male		Males
D008845	Microinjections	The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes.	Microinjection
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009619	Nociceptors	Peripheral AFFERENT NEURONS which are sensitive to injuries or pain, usually caused by extreme thermal exposures, mechanical forces, or other noxious stimuli. Their cell bodies reside in the DORSAL ROOT GANGLIA. Their peripheral terminals (NERVE ENDINGS) innervate target tissues and transduce noxious stimuli via axons to the CENTRAL NERVOUS SYSTEM.	Pain Receptors,Receptors, Pain,Nociceptive Neurons,Neuron, Nociceptive,Neurons, Nociceptive,Nociceptive Neuron,Nociceptor,Pain Receptor
D010147	Pain Measurement	Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies.	Analgesia Tests,Analogue Pain Scale,Formalin Test,McGill Pain Questionnaire,Nociception Tests,Pain Assessment,Pain Intensity,Pain Severity,Tourniquet Pain Test,Visual Analogue Pain Scale,Analog Pain Scale,Assessment, Pain,McGill Pain Scale,Visual Analog Pain Scale,Analgesia Test,Analog Pain Scales,Analogue Pain Scales,Formalin Tests,Intensity, Pain,Measurement, Pain,Nociception Test,Pain Assessments,Pain Intensities,Pain Measurements,Pain Questionnaire, McGill,Pain Scale, Analog,Pain Scale, Analogue,Pain Scale, McGill,Pain Severities,Pain Test, Tourniquet,Questionnaire, McGill Pain,Scale, Analog Pain,Scale, Analogue Pain,Scale, McGill Pain,Severity, Pain,Test, Analgesia,Test, Formalin,Test, Nociception,Test, Tourniquet Pain,Tests, Nociception,Tourniquet Pain Tests
D010487	Periaqueductal Gray	Central gray matter surrounding the CEREBRAL AQUEDUCT in the MESENCEPHALON. Physiologically it is probably involved in RAGE reactions, the LORDOSIS REFLEX; FEEDING responses, bladder tonus, and pain.	Mesencephalic Central Gray,Midbrain Central Gray,Central Gray Substance of Midbrain,Central Periaqueductal Gray,Griseum Centrale,Griseum Centrale Mesencephali,Periaqueductal Gray Matter,Substantia Grisea Centralis,Substantia Grisea Centralis Mesencephali,Central Gray, Mesencephalic,Central Gray, Midbrain,Gray Matter, Periaqueductal,Gray, Central Periaqueductal,Griseum Centrale Mesencephalus,Periaqueductal Grays, Central
D011930	Reaction Time	The time from the onset of a stimulus until a response is observed.	Response Latency,Response Speed,Response Time,Latency, Response,Reaction Times,Response Latencies,Response Times,Speed, Response,Speeds, Response
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260	Female		Females