title: Procedure of bidirectional selective outbreeding for production of two rat lines differing in sensitivity to the sedative/hypnotic effect of gamma-hydroxybutyric acid.
abstract: The exogenous administration of gamma-hydroxybutyric acid (GHB), a constituent of the mammalian brain where it likely functions as a neurotransmitter or a neuromodulator, exerts a number of pharmacological effects, including sedation and hypnosis. The present paper describes a procedure for selective breeding of two rat lines which markedly differ in sensitivity to the sedative/hypnotic effect of GHB. Selective breeding originated from Wistar rats showing opposite sensitivity to the sedative/hypnotic effect of 1 g/kg GHB (i.p.). 'Sensitive' Wistar rats, defined as those individuals displaying values of r = sleep time/onset greater than the upper 15th percentile, were mated to generate the GHB-sensitive (GHB-S) line; conversely, 'resistant' Wistar rats (r-values lower than the lower 15th percentile) were mated to generate the GHB-resistant (GHB-R) line. Upper and lower 15th percentiles were also used to establish the selection cut-offs and criteria for rats of subsequent generations. Specifically, r-values of GHB-S rats were required to be r > or =8 on two separate tests with GHB; r-values of GHB-R rats were required to be r < or =2 on two separate tests with GHB. In each of the three generations produced to date, GHB-S rats showed significantly shorter onset, longer sleep times and greater r-scores than GHB-R rats. The selective breeding of GHB-S and GHB-R rats: (a) suggests that sensitivity to GHB is under genetic control, and (b) may constitute a unique model for investigation of the physiological function of GHB.
authors.affiliation: 'Bernard B. Brodie' Department of Neuroscience, University of Cagliari, S.S. 554, Km. 4.5, I-09042 (CA), Monserrato, Italy
authors.forename: C
authors.initials: C
authors.lastname: Lobina
authors.forename: G
authors.initials: G
authors.lastname: Colombo
authors.forename: G
authors.initials: G
authors.lastname: Brunetti
authors.forename: G
authors.initials: G
authors.lastname: Diaz
authors.forename: S
authors.initials: S
authors.lastname: Melis
authors.forename: M
authors.initials: M
authors.lastname: Pani
authors.forename: S
authors.initials: S
authors.lastname: Serra
authors.forename: G
authors.initials: G
authors.lastname: Vacca
authors.forename: G L
authors.initials: GL
authors.lastname: Gessa
authors.forename: M A
authors.initials: MA
authors.lastname: Carai
mesh_terms: D000822:Animal Husbandry / Q000379:methods*; D000818:Animals; D004351:Drug Resistance; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D051381:Rats / Q000235:genetics* / Q000502:physiology; D017208:Rats, Wistar; D012978:Sodium Oxybate / Q000494:pharmacology*
chemical_list: D006993:Hypnotics and Sedatives; D012978:Sodium Oxybate