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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 95 (1988), S. 38-42 
    ISSN: 1432-2072
    Keywords: SL 75102 ; THIP ; Lorazepam ; GABA ; Benzodiazepine ; Schedule-controlled behavior ; Monkeys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 129 (1997), S. 1-14 
    ISSN: 1432-2072
    Keywords: Key words Caffeine ; Xanthines ; Adenosine antagonist ; Phosphodiesterase inhibition ; Operant behavior ; Respiration ; Cardiovascular system ; Nonhuman primates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Caffeine and related xanthines can have significant behavioral effects on measures of locomotor activity, schedule-controlled behavior, drug self-administration, and learning and memory. Xanthines also produce numerous physiological effects including positive inotropic and chronotropic effects on the heart, decreased airway resistance in the lung, and respiratory stimulation. Due to the widespread use of xanthines as constituents of food and beverages and as therapeutic drugs, identification of mechanisms that mediate their pharmacological effects has considerable relevance for drug development and therapeutics. Two primary mechanisms involving the cyclic nucleotide system have been implicated as the bases for the effects of xanthines in the CNS. Many xanthines bind to specific adenosine recognition sites and block the actions of adenosine. Xanthines also inhibit cyclic nucleotide phosphodiesterases, the enzymes responsible for the hydrolytic inactivation of cyclic AMP and cyclic GMP. Recent research in nonhuman primates has characterized the behavioral, respiratory and cardiovascular effects of a number of xanthines and related drugs differing in affinity at different subtypes of adenosine receptors and in capacity to inhibit different molecular forms of PDE. The behavioral-stimulant effects of xanthines appear to be mediated principally by their adenosine-antagonist actions and may be limited by PDE inhibition. The respiratory-stimulant and cardiac effects of xanthines, on the other hand, appear to be linked more closely to their PDE- inhibiting actions than to adenosine antagonism. Converging lines of evidence suggest that adenosine A2 and cAMP-specific (possibly type IV) PDE mechanisms play especially prominent roles in mediating the behavioral and physiological effects of xanthines in nonhuman primates.
    Type of Medium: Electronic Resource
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