ISSN:
1432-2072
Schlagwort(e):
SL 75102
;
THIP
;
Lorazepam
;
GABA
;
Benzodiazepine
;
Schedule-controlled behavior
;
Monkeys
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Abstract The behavioral effects of the GABA-related drugs SL 75102 (4-{[(4-chlorophenyl)-(5-fluoro-2-hydroxyphenyl)-methylene]amino}butyric acid) and THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyrindin-3-ol) were studied alone and in combination with lorazepam. Two groups of squirrel monkeys responded under a fixed-interval schedule of food presentation. In one group, responding was suppressed by superimposing a fixed-ratio schedule of response-produced electric shock; responding was not suppressed in the second group. Dose-response curves were determined by administering cumulative doses IV during timeout periods that preceded sequential components of the fixed-interval schedule. Neither SL 75102 (1.0–30.0 mg/kg) nor THIP (0.1–3.0 mg/kg) significantly altered rates of either suppressed or nonsuppressed responding, whereas lorazepam (0.01–0.3 mg/kg) produced dose-related increases in response rate under both schedules. Pretreatment with 1.0 mg/kg SL 75102 significantly enhanced the rate-increasing effects of lorazepam on suppressed responding. Pretreatment with 10.0 mg/kg SL 75102 also enhanced the rate-increasing effects of lorazepam on nonsuppressed responding. In contrast, the rate-increasing effects of lorazepam were not enhanced by pretreatment with 0.3 or 1.0 mg/kg THIP under either schedule. Moreover, pretreatment with 1.0 mg/kg THIP attenuated the rate-increasing effects of lorazepam on nonsuppressed responding. Enhancement of the behavioral effects of lorazepam by SL 75102 may reflect positive allosteric interactions between the two drugs at the benzodiazepine-GABA receptor complex.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00212763
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