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  • 1
    Electronic Resource
    Electronic Resource
    Gilbert and Descartes: The science of conserving the compound body (1982)
    Springer
    Journal for general philosophy of science 13 (1982), S. 224-233 
    Details
    ISSN: 1572-8587
    Source: Springer Online Journal Archives 1860-2000
    Topics: Philosophy , Nature of Science, Research, Systems of Higher Education, Museum Science
    Notes: Summary We shall proceed as follows: In section ii, we shall give a brief over-view of the literature on Gilbert, more to indicate general directions of interest than to present any in-depth analysis. Then, in the main body of this presentation, section iii, we will present three ways in which we think it is accurate to claim that Gilbert influenced Descartes. These are: (1) Gilbert gave Descartes a new definition of an organ; (2) Gilbert gave Descartes a new definition of what constitutes life and animation; (3) Gilbert gave Descartes a new view of natural motion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01801557
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  • 2
    Electronic Resource
    Electronic Resource
    Discriminative stimulus properties of d-amphetamine-pentobarbital combinations (1980)
    Springer
    Psychopharmacology 68 (1980), S. 269-276 
    Details
    ISSN: 1432-2072
    Keywords: d-Amphetamine ; Pentobarbital ; Drug interactions ; Discriminative stimulus properties of drugs ; Discrimination history ; Key peck ; Pigeons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pigeons were trained to discriminate IM injections of 1.0 mg/kg d-amphetamine from water, 5.6 mg/kg pentobarbital from water, or 1.0 mg/kg d-amphetamine from 5.6 mg/kg pentobarbital by requiring them to peck different response keys depending on which substance was administered prior to the session. Excellent stimulus control was achieved under all conditions with close to 100% of the responses occurring on the injection-correlated key. In tests with doses different from those used in training, the percentage of responses on the drug key was directly related to drug dose. When d-amphetamine was given to birds trained to discriminate pentobarbital from water or when pentobarbital was given to birds trained to discriminate d-amphetamine from water, responding occurred predominately on the water-correlated key. d-Amphetamine produced a dose-related antagonism of the effects of pentobarbital for birds trained to discriminate pentobarbital from water or from d-amphetamine. Rates of responding on the drug key were generally highes after administration of the drug doses used in discrimination training; but response rates were not systematically related to the percentage of responses occurring on the drug key. All birds were subsequently trained to discriminate a combination of 1.0 mg/kg d-amphetamine and 5.6 mg/kg pentobarbital from either 1.0 mg/kg d-amphetamine or 5.6 mg/kg pentobarbital alone, demonstrating that the discriminative stimulus properties of amphetamine-pentobarbital combinations are different from either drug alone. Several of the drug effects reported were related to the drug discrimination that had been established.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428114
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  • 3
    Electronic Resource
    Electronic Resource
    Discriminative stimulus properties of naloxone (1982)
    Springer
    Psychopharmacology 77 (1982), S. 305-308 
    Details
    ISSN: 1432-2072
    Keywords: Naloxone ; Opioid antagonists ; Drug discrimination ; Pigeons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nonopioid-dependent pigeons were trained to discriminate IM injections of 30.0 mg/kg naloxone from water in a procedure in which 15 consecutive responses on one of two keys resulted in grain presentation. Naloxone-appropriate responding was maximal at doses of naloxone equal to and greater than the training dose. The onset of the naloxone discriminative cue was rapid (less than 5 min) and the duration of the cue was short (less than 60 min). Naltrexone (1.0–10.0 mg/kg), pentazocine (1.0–10.0 mg/kg), levallorphan (1.0–30.0 mg/kg), and nalorphine (3.0–30.0 mg/kg) produced dose-dependent increases in naloxone-appropriate responding, occasioning 100% naloxone-key selections. In contrast, cyclazocine, profadol, and diprenorphine, at doses up to those at which animals did not respond, produced only intermediate degrees of naloxone-appropriate responding. Morphine always produced selection of the water key. These results demonstrate that a pure opioid antagonist, such as naloxone, has discriminative stimulus effects in the nonopioid-dependent animal, that these stimulus effects are shared by certain other opioid antagonists, and that these effects are distinguishable from those produced by pure opioid agonists, such as morphine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432760
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  • 4
    Electronic Resource
    Electronic Resource
    Reinforcing and discriminative stimulus effects of the neuroactive steroids pregnanolone and Co 8-7071 in rhesus monkeys (1999)
    Springer
    Psychopharmacology 145 (1999), S. 205-212 
    Details
    ISSN: 1432-2072
    Keywords: Key words Neuroactive steroid ; Barbiturate ; Self-administration ; Discriminative stimulus effects ; Rhesus monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale and Objectives: The present study was designed to assess possible abuse-related effects of the endogenous neuroactive steroid pregnanolone (3α-hydroxy-5β-pregnan-20-one) and the orally bioavailable, water-soluble neuroactive steroid pro-drug Co 8-7071 (3α,21-dihydroxy-3β-trifluoromethyl-5β-pregnan-20-one, 21-hemisuccinate). Methods: Four rhesus monkeys were prepared with chronic intravenous (IV) catheters and trained to press a lever under a ten-response fixed-ratio (FR) schedule of methohexital injection (0.1 mg/kg per injection). Three rhesus monkeys were trained to discriminate intragastric infusions of pentobarbital (10 mg/kg) from saline infusions under a FR5 schedule of stimulus-shock termination. Results: At least two doses of pregnanolone (0.003–0.1 mg/kg per injection) maintained injections per session above saline levels in the four monkeys tested, whereas Co 8-7071 (0.01–1.0 mg/kg per injection) maintained injections per session above saline levels in two of four monkeys at relatively low levels of injections per session. In rhesus monkeys trained to discriminate pentobarbital, IV pregnanolone injections (0.1–1.7 mg/kg, 5-min presession) dose-dependently reproduced the discriminative stimulus effects of pentobarbital in all monkeys tested. Intravenous administration of Co 8-7071 (1–10 mg/kg, 5-min presession) resulted in a dose-dependent increase to 〉80% pentobarbital-appropriate responding in two of three monkeys tested. Following intragastric infusions of Co 8-7071 (1.0–30 mg/kg), ≥80% pentobarbital-appropriate responding occurred in one out of three monkeys at 10 mg/kg when administered 60 min before the session. When administered 120 min before the session, however, 10–30 mg/kg Co 8-7071 reproduced the discriminative stimulus effects of pentobarbital in each of the three monkeys tested. Conclusions: These data demonstrate barbiturate-like abuse-related effects that differed between two pregnane steroids. Whereas pregnanolone functioned as a reinforcer, suggesting that this compound has abuse potential, Co 8-7071 did not, despite having pentobarbital-like discriminative effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130051050
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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacological evaluation of a modified conflict procedure: punished drinking in non-water-deprived rats (1999)
    Springer
    Psychopharmacology 145 (1999), S. 333-341 
    Details
    ISSN: 1432-2072
    Keywords: Key words Anxiolytic ; Anxiety ; Benzodiazepine ; GABAA ; 5-HT1A ; Neuroactive steroid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Conflict procedures used to detect anxiolytic-like activity of drugs often rely on maintaining strict schedules of water or food availability. It is ethically and practically desirable to reduce such states of deprivation in animal testing. Objective: The purpose of the present experiment was to develop and pharmacologically characterize a conflict drinking procedure that did not require the use of water-deprived animals. Methods: Rats were tested during daily sessions with alternating unpunished drinking (no tone: lick=sucrose solution) and signaled punished drinking (tone: lick=sucrose+shock) components, and developed individual steady baselines over a brief training period (approximately 3–4 weeks). The drugs tested i.p. were the positive allosteric modulators of γ-amino butyric acidA (GABA)A receptors, diazepam (0.03–30 mg/kg), chlordiazepoxide (0.03–30 mg/kg), lorazepam (0.03–10 mg/kg), zolpidem (0.3–10 mg/kg), pentobarbital (1–30 mg/kg), pregnanolone (1–30 mg/kg), and bretazenil (0.03– 10 mg/kg); the 5-hydroxy tryptamine1A (HT)1A-mediated anxiolytics, buspirone (1–10 mg/kg) and ipsapirone (1–17 mg/kg); and the negative controls d-amphetamine (0.3–3 mg/kg), haloperidol (0.01–0.3 mg/kg), morphine (0.3–17 mg/kg), and imipramine (0.3–30 mg/kg). Results: The experimental procedure was sensitive to increases in punished drinking by the GABAA-positive modulators, consistent with their known or putative anxiolytic activity. Further, the 5-HT1A-mediated anxiolytics increased punished drinking, although to a lesser extent and over a more narrow dose range than did the GABAergic drugs. In contrast, d-amphetamine, haloperidol, morphine, and imipramine failed to increase punished drinking up to doses that decreased unpunished drinking. Conclusions: The present results indicate that water deprivation is not a necessary condition to engender drinking conflict behavior or to obtain pharmacological effects similar to those obtained with other classical conflict procedures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130051066
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  • 6
    Electronic Resource
    Electronic Resource
    Positive allosteric modulators of the GABAA receptor: differential interaction of benzodiazepines and neuroactive steroids with ethanol (1999)
    Springer
    Psychopharmacology 141 (1999), S. 77-82 
    Details
    ISSN: 1432-2072
    Keywords: Key words Allopregnanolone ; Pregnanolone ; Neurosteroid ; Neuroactive steroid ; Motor behavior ; Ethanol interaction ; Benzodiazepine ; Triazolam ; Diazepam
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Endogenous pregnane steroids, such as allopregnanolone (3α-hydroxy-5α-pregnan-20-one; 3α, 5α-P) and pregnanolone (3α-hydroxy-5β-pregnan-20-one; 3α,5β-P), allosterically modulate GABAA receptor function and exhibit behavioral effects similar to benzodiazepines, though acting at a distinct recognition site. Inasmuch as some positive allosteric modulators of GABAA receptor function exhibit profound interactions with ethanol, the effects of 3α,5α-P and 3α,5β-P were compared to those of two benzodiazepines, triazolam and diazepam, on the motor function of mice and rats when administered either alone or in combination with ethanol. All four test compounds exhibited dose-related impairment of motor function in the horizontal wire task in mice and the rotorod task in rats. Ethanol caused a marked enhancement of triazolam- and diazepam-induced motor impairment. In contrast, ethanol enhanced to a lesser extent the motor impairment induced by both neurosteroids in mice and not at all in rats. All four compounds increased ethanol-induced behavioral sleep time in mice, although the benzodiazepines did so at a much smaller fraction of their ataxic doses as compared to the neurosteroids. As one of the undesired side-effects of therapeutic use of benzodiazepines is their interaction with ethanol, development of neuroactive steroids as drugs may offer therapeutic advantages.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050809
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  • 7
    Electronic Resource
    Electronic Resource
    Neuroactive steroids attenuate cocaine-induced sucrose intake in rats, but not cocaine-induced hyperactivity in mice (2000)
    Springer
    Psychopharmacology 149 (2000), S. 269-276 
    Details
    ISSN: 1432-2072
    Keywords: Key words Neurosteroid ; Cocaine ; Ganaxolone ; Co 2-1068 ; Haloperidol ; Locomotion ; Food intake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Neuroactive steroids, including the potent anticonvulsants ganaxolone (3α-hydroxy-3β-methyl-5α-pregnan-20-one) and Co 2-1068 (3β-(4acetylphenyl)ethynyl-3α,21-dihydroxy-5β-20-one-21-hemisuccinate), have recently been shown to protect against cocaine-induced seizures. Objectives: The purpose of the present experiments was to determine whether ganaxolone and Co 2-1068 attenuate acute behavioral effects of cocaine unrelated to seizures. Methods: In the first experiment, the locomotor effects of Co 2-1068 (10–100 mg/ kg), pentobarbital (10–100 mg/kg) and haloperidol (0.03–0.3 mg/kg), alone or in combination with cocaine (5.6–30 mg/kg), were determined in mice. In the second experiment, the effects on sucrose intake of ganaxolone (4–16 mg/kg), Co 2-1068 (8–64 mg/kg), pentobarbital (4–32 mg/kg), and haloperidol (0.04–0.4 mg/kg), alone or in combination with cocaine (4–16 mg/kg), were determined in rats. Results: Cocaine caused a dose-related increase in locomotor activity in mice, whereas Co 2-1068, pentobarbital and haloperidol caused dose-related decreases. The dopamine antagonist haloperidol, at a dose that had no effect on activity by itself, but not Co 2-1068 or pentobarbital, attenuated the cocaine-induced increase in locomotor activity. Cocaine, ganaxolone, Co 2-1068, and haloperidol produced dose-related decreases in sucrose intake in rats; the effects of pentobarbital on sucrose intake were variable. As with locomotor effects, haloperidol attenuated the cocaine-induced decrease in sucrose intake. In addition, cocaine-induced decreases in sucrose intake were attenuated by ganaxolone and Co 2-1068. Pentobarbital had no statistically significant effect on the cocaine dose-response function. Conclusions: These results suggest that the interaction of neuroactive steroids with cocaine extends to pharmacologic actions beyond anticonvulsant efficacy, but that the blockade of behavioral effects of cocaine by neuroactive steroids does not apply to all acute behaviors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002139900350
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