Gamma butyrolactone (GBL) and gamma valerolactone (GVL): Similarities and differences in their effects on the acoustic startle reflex and the conditioned enhancement of startle in the rat
| Autor: | Bonita J. Leavell, Calleen M. Jones, Laureen J. Marinetti, Daniel S. Isenschmid, Randall L. Commissaris, Bradford R. Hepler |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Reflex Startle genetic structures Conditioning Classical Clinical Biochemistry Startle amplitude Pharmacology Toxicology Biochemistry Rats Sprague-Dawley Lactones Behavioral Neuroscience chemistry.chemical_compound 4-Butyrolactone immune system diseases Animals Prodrugs Biological Psychiatry gamma-Butyrolactone Dose-Response Relationship Drug Brain Gamma hydroxybutyrate Long-term potentiation Rats gamma-Valerolactone Dose–response relationship surgical procedures operative Receptors GABA-B chemistry Acoustic Startle Reflex Anesthesia Reflex Sodium Oxybate |
| Zdroj: | Pharmacology Biochemistry and Behavior. 101:602-608 |
| ISSN: | 0091-3057 |
| DOI: | 10.1016/j.pbb.2012.01.023 |
| Popis: | Gamma butyrolactone (GBL) is metabolized to gamma hydroxybutyrate (GHB) in the body. GHB is a DEA Schedule 1 compound; GBL is a DEA List 1 chemical. Gamma valerolactone (GVL) is the 4-methyl analog of GBL; GVL is metabolized to 4-methyl-GHB; GVL is NOT metabolized to GBL or GHB. The effects of GBL (18.75-150 mg/kg), GVL (200-1600 mg/kg) or vehicle on the acoustic startle reflex (ASR), and the classically-conditioned enhancement of startle, the Startle Anticipated Potentiation of Startle (SAPS) response were studied in male rats. Both compounds produced a dose-dependent reduction of ASR, with GBL 5-7 times more potent than GVL. In contrast, GBL treatment significantly reduced SAPS at doses that exerted only moderate effects on ASR, whereas GVL exerted little or no effect on the SAPS, except at doses that produced pronounced reductions in Noise Alone ASR. In a second experiment, rats were tested for Noise Alone ASR behavior following treatment with a single mid-range dose of GBL (75 mg/kg), GVL (400mg/kg) or vehicle; immediately following startle testing the animals were sacrificed and their brains and blood were collected for determination of GHB, 4-methyl-GHB, GBL and GVL. GHB was found in measurable concentrations in all of the blood specimens and 6 (of 8) of the brain specimens from the GBL-treated subjects. 4-Methyl-GHB was found in measurable concentrations in all of the blood and brain specimens of the GVL-treated subjects; the change in startle amplitude was inversely correlated to the brain concentrations of these compounds. These findings confirm the differences in the metabolic fate of GBL and GVL as pro-drugs for the formation of GHB and 4-methyl-GHB, respectively. Moreover, the dissimilarity in effect profile for GBL and GVL on ASR versus SAPS behaviors suggests that different receptor(s) may be involved in mediating these behavioral effects. |
| Databáze: | OpenAIRE |
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