title: Effects of lorazepam on short latency afferent inhibition and short latency intracortical inhibition in humans.
abstract: Experimental studies have demonstrated that the GABAergic system modulates acetylcholine release and, through GABA(A) receptors, tonically inhibits cholinergic activity. Little is known about the effects of GABA on the cholinergic activity in the human central nervous system. In vivo evaluation of some cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with TMS of the motor cortex. Peripheral nerve inputs have an inhibitory effect on motor cortex excitability at short intervals (short latency afferent inhibition, SAI). We investigated whether GABA(A) activity enhancement by lorazepam modifies SAI. We also evaluated the effects produced by lorazepam on a different TMS protocol of cortical inhibition, the short interval intracortical inhibition (SICI), which is believed to be directly related to GABA(A) activity. In 10 healthy volunteers, the effects of lorazepam were compared with those produced by quetiapine, a psychotropic drug with sedative effects with no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors, and with those of a placebo using a randomized double-blind study design. Administration of lorazepam produced a significant increase in SICI (F(3,9) = 3.19, P = 0.039). In contrast to SICI, SAI was significantly reduced by lorazepam (F(3,9) = 9.39, P = 0.0002). Our findings demonstrate that GABA(A) activity enhancement determines a suppression of SAI and an increase of SICI.
authors.affiliation: Istituto di Neurologia, Università Cattolica, L.go A. Gemelli 8, 00168 Rome, Italy. vdilazzaro@rm.unicatt.it
authors.forename: V
authors.initials: V
authors.lastname: Di Lazzaro
authors.forename: A
authors.initials: A
authors.lastname: Oliviero
authors.forename: E
authors.initials: E
authors.lastname: Saturno
authors.forename: M
authors.initials: M
authors.lastname: Dileone
authors.forename: F
authors.initials: F
authors.lastname: Pilato
authors.forename: R
authors.initials: R
authors.lastname: Nardone
authors.forename: F
authors.initials: F
authors.lastname: Ranieri
authors.forename: G
authors.initials: G
authors.lastname: Musumeci
authors.forename: T
authors.initials: T
authors.lastname: Fiorilla
authors.forename: P
authors.initials: P
authors.lastname: Tonali
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D004311:Double-Blind Method; D004574:Electromagnetic Fields; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008140:Lorazepam / Q000494:pharmacology*; D009044:Motor Cortex / Q000187:drug effects* / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
chemical_list: D008140:Lorazepam
references.citation: J Physiol. 2000 Mar 1;523 Pt 2:503-13
references.pmid: 10699092
references.citation: J Neurol Neurosurg Psychiatry. 2005 Aug;76(8):1064-9
references.pmid: 16024879
references.citation: Eur J Neurosci. 2000 Jun;12(6):1941-8
references.pmid: 10886335
references.citation: Exp Brain Res. 2000 Dec;135(4):455-61
references.pmid: 11156309
references.citation: J Physiol. 2001 Jan 15;530(Pt 2):307-17
references.pmid: 11208978
references.citation: Neurology. 2002 Aug 13;59(3):392-7
references.pmid: 12177373
references.citation: Brain Res. 2002 Nov 22;956(1):81-5
references.pmid: 12426049
references.citation: J Physiol. 2002 Nov 15;545(Pt 1):153-67
references.pmid: 12433957
references.citation: Eur J Neurosci. 2003 Jan;17(2):249-59
references.pmid: 12542661
references.citation: Exp Clin Psychopharmacol. 2003 Feb;11(1):56-72
references.pmid: 12622344
references.citation: Neuroreport. 2003 Apr 15;14(5):773-6
references.pmid: 12692481
references.citation: Brain. 2003 Aug;126(Pt 8):1883-94
references.pmid: 12805105
references.citation: Clin Neurophysiol. 2003 Oct;114(10):1834-40
references.pmid: 14499745
references.citation: Psychopharmacology (Berl). 2003 Nov;170(3):255-62
references.pmid: 12904966
references.citation: Exp Brain Res. 2004 Jan;154(1):1-10
references.pmid: 14579004
references.citation: Clin Neurophysiol. 2004 Feb;115(2):255-66
references.pmid: 14744565
references.citation: J Neurol Neurosurg Psychiatry. 2004 Apr;75(4):555-9
references.pmid: 15026495
references.citation: Brain. 2004 Apr;127(Pt 4):E8; author reply E9
references.pmid: 15044312
references.citation: J Neurophysiol. 2004 Jul;92(1):66-72
references.pmid: 14724259
references.citation: Clin Neurophysiol. 2004 Aug;115(8):1717-29
references.pmid: 15261850
references.citation: Proc Natl Acad Sci U S A. 1985 Sep;82(18):6344-8
references.pmid: 3862134
references.citation: J Comp Neurol. 1986 Aug 15;250(3):282-95
references.pmid: 3528237
references.citation: J Physiol. 1986 Jun;375:169-94
references.pmid: 2879035
references.citation: Synapse. 1991 Feb;7(2):151-68
references.pmid: 1672782
references.citation: Trends Neurosci. 1993 Jun;16(6):218-22
references.pmid: 7688162
references.citation: J Physiol. 1993 Nov;471:501-19
references.pmid: 8120818
references.citation: Exp Brain Res. 1996 Apr;109(1):127-35
references.pmid: 8740215
references.citation: Ann Neurol. 1996 Sep;40(3):367-78
references.pmid: 8797526
references.citation: Electroencephalogr Clin Neurophysiol. 1997 Dec;105(6):430-7
references.pmid: 9448644
references.citation: Neuroscience. 1998 Oct;86(3):937-47
references.pmid: 9692729
references.citation: Science. 1998 Aug 14;281(5379):985-8
references.pmid: 9703513
references.citation: Electroencephalogr Clin Neurophysiol. 1998 Oct;109(5):426-35
references.pmid: 9851300
references.citation: Clin Neurophysiol. 2000 May;111(5):794-9
references.pmid: 10802448