title: Serotonergic modulation of neuronal activity in rat midbrain periaqueductal gray.
abstract: Serotonin (5-HT) modulates pain and anxiety from within the midbrain periaqueductal gray (PAG). In the present study, the effects of 5-HT- and 5-HT(1/2) subtype-selective ligands on rat PAG neurons were examined using whole cell patch-clamp recordings in brain slices. In voltage clamp, 5-HT produced outward and inward currents in distinct subpopulations of neurons that varied throughout different subregions of the PAG. The 5-HT(1A) agonist R(+)-8-OH-DPAT (1 μM) produced outward currents in subpopulations of PAG neurons. By contrast, sumatriptan (1 μM) and other 5-HT(1B, -D), and (-F) subtype agonists had little or no postsynaptic activity. The 5-HT(2A/C) agonists DOI (3 μM) and TCB-2 (1 μM) produced inward currents in subpopulations of PAG neurons, and DOI enhanced evoked inhibitory postsynaptic currents via a presynaptic mechanism. In current clamp, both R(+)-8-OH-DPAT and sumatriptan produced an excitatory increase in evoked mixed postsynaptic potentials (PSPs). In addition, R(+)-8-OH-DPAT, but not sumatriptan, directly hyperpolarized PAG neurons. By contrast, the 5-HT(2) agonist DOI depolarized subpopulations of neurons and produced an inhibitory decrease in evoked mixed PSPs. These findings indicate that 5-HT(1A) and 5-HT(1B/D) ligands have partly overlapping inhibitory effects on membrane excitability and synaptic transmission within the PAG, which are functionally opposed by 5-HT(2A/C) actions in specific PAG subregions.
authors.affiliation: Pain Management Research Institute, Kolling Institute of Medical Research, Northern Clinical School, Univ. of Sydney at Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Jeong
authors.forename: Karen
authors.initials: K
authors.lastname: Lam
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Mitchell
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Vaughan
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010487:Periaqueductal Gray / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D018490:Serotonin Agents / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology
chemical_list: D018490:Serotonin Agents; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D018170:Sumatriptan
keywords: IPSP; PAG; postsynaptic; presynaptic; serotonin