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  • 1
    Electronic Resource
    Electronic Resource
    Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress (2000)
    [s.l.] : Nature America Inc.
    Nature genetics 24 (2000), S. 410-414 
    Details
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Corticotropin-releasing hormone (Crh) is a critical coordinator of the hypothalamic-pituitary-adrenal (HPA) axis. In response to stress, Crh released from the paraventricular nucleus (PVN) of the hypothalamus activates Crh receptors on anterior pituitary corticotropes, resulting in release of ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/74263
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  • 2
    Electronic Resource
    Electronic Resource
    A role for the mesolimbic dopamine system in the psychostimulant actions of MDMA (1989)
    Springer
    Psychopharmacology 99 (1989), S. 40-47 
    Details
    ISSN: 1432-2072
    Keywords: Methylenedioxymethamphetamine ; MDMA ; Nucleus accumbens ; Locomotor activity ; Mesolimbic dopamine ; 6-Hydroxydopamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Methylenedioxymethamphetamine (MDMA) is a phenylethylamine with a chemical structure that resembles both the amphetamines and mescaline and has both stimulant and perception altering properties. The stimulant properties of MDMA were assessed in photocell cages designed to measure locomotor activity in rats. MDMA, over a range of doses (2.5–10.0 mg/kg, SC) produced locomotor hyperactivity which lasted up to 4 h. Further studies examined the role of the mesolimbic dopamine system in the hyperactivity induced by MDMA. 6-Hydroxydopamine lesions of the Nucleus accumbens attenuated the locomotor response produced by MDMA. The well characterized attenuation of the locomotor response produced by amphetamine was also demonstrated in the same rats. The present study demonstrates similarities in the stimulant properties of MDMA and amphetamine, and also suggests that as with amphetamine, the locomotor activation associated with MDMA may involve the presynaptic release of dopamine in the region of the Nucleus accumbens. However, MDMA may have a more unusual pharmacological profile because of its longer duration of action, neurotoxic potential, and differences in the qualitative aspects of its psychoactive effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00634450
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  • 3
    Electronic Resource
    Electronic Resource
    MDMA produces stimulant-like conditioned locomotor activity (1989)
    Springer
    Psychopharmacology 99 (1989), S. 352-356 
    Details
    ISSN: 1432-2072
    Keywords: Conditioned locomotion ; MDMA ; Aniphetamine ; Cocaine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Daily administration of a drug in a distinctive environment establishes contingencies that support Pavlovian conditioning. Environmental cues that are paired with the drug injection and that predict the onset of drug action can become conditioned stimuli. Ultimately, the conditioned stimuli come to predict the availability of drug and develop the potential to engender conditioned drug responses. Various psychostimulant drugs can produce conditioned locotnotion when tested in the presence of environmental cues that were repeatedly associated with the drug experience. The ability of amphetamine and cocaine to produce conditioned locomotion was demonstrated in the present study. Stimulant-like properties of methylenedioxymethamphetamine (MDMA) have been reported in locomotor paradigms, drug discrimination procedures, and human subjective questionnaires. MDMA (5 mg/kg), paired for 5 days to a distinct environment signalled by the presence of a distinct odor, produced enhanced locomotion during a test probe with the odor alone indicating that MDMA can also produce conditioned locomotion. The observation that the stimulus properties of MDMA can also become associated with environmental cues supports the hypothesis that some of the behavioral effects of MDMA resemble those of other classical psychostimulants such as amphetamine and cocaine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00445556
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  • 4
    Electronic Resource
    Electronic Resource
    The acoustic startle response as a measure of behavioral dependence in rats (1992)
    Springer
    Psychopharmacology 108 (1992), S. 40-46 
    Details
    ISSN: 1432-2072
    Keywords: Physical dependence ; Acoustic startle response ; Withdrawal ; Morphine ; Naloxone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A series of experiments was conducted to assess the sensitivity of the acoustic startle response to chronic morphine administration and naloxone-precipitated withdrawal. Rats were implanted with two subcutaneous pellets containing either 75 mg each of morphine or containing only placebo. In experiment 1, withdrawal induced by 0.05–0.2 mg/kg naloxone dose-dependently decreased the magnitude of the startle response. Physical dependence was confirmed by a naloxone-induced acute weight loss seen in morphine-implanted rats, but naloxone had no effect on startle or body weight in nondependent animals. In experiment 2, a modified procedure with fewer trials per session and fewer test days was employed. Naloxone (0.2 mg/kg) given 4–5 days after implantation induced large startle-response decreases in morphine-dependent rats while having no effect in placebo-implanted rats. Post-naloxone saline tests revealed no significant differences in startle between morphine and placebo groups. Startle scores were significantly higher in morphine-implanted rats than in placebo rats during a saline test given 3 days following pellet implantation. In a separate group of animals, however, acute IP injections of morphine from 0.3–10 mg/kg had no significant effect on startle amplitude. The effect of repeated pairings of withdrawal with the startle environment was assessed in experiment 3. Morphine-dependent rats startled significantly less if naloxone injections were given before the startle session than if they were administered 4 h later. Conditioned withdrawal effects, expressed during a final test session when all rats received saline, were observed for the body-weight measure but not for the startle response. These results suggest that the acoustic startle response may be a useful objective measure in evaluating physical dependence produced by substances of abuse.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245283
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  • 5
    Electronic Resource
    Electronic Resource
    Animal models of drug craving (1993)
    Springer
    Psychopharmacology 112 (1993), S. 163-182 
    Details
    ISSN: 1432-2072
    Keywords: Drug craving ; Addiction ; Drug dependence ; Incentive-motivation ; Animal models ; Validity ; Reliability ; Progressive ratio ; Choice ; Second-order schedule ; Extinction ; Conditioned reinforcement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Drug craving, the desire to experience the effect(s) of a previously experienced psychoactive substance, has been hypothesized to contribute significantly to continued drug use and relapse after a period of abstinence in humans. In more theoretical terms, drug craving can be conceptualized within the framework of incentive motivational theories of behavior and be defined as the incentive motivation to self-administer a psychoactive substance. The incentive-motivational value of drugs is hypothesized to be determined by a continuous interaction between the hedonic rewarding properties of drugs (incentive) and the motivational state of the organism (organismic state). In drug-dependent individuals, the incentive-motivational value of drugs (i.e., drug craving) is greater compared to non-drug-dependent individuals due to the motivational state (i.e., withdrawal) developed with repeated drug administration. In this conceptual framework, animal models of drug craving would reflect two aspects of the incentive motivation to self-administer a psychoactive substance. One aspect would be the unconditioned incentive (reinforcing) value of the drug itself. The other aspect would be relatively independent of the direct (unconditioned) incentive value of the drug itself and could be reflected in the ability of previously neutral stimuli to acquire conditioned incentive properties that could elicit drug-seeking and drug-taking behavior. Animal models of drug craving that permit the investigation of the behavioral and neurobiological components of these two aspects of drug craving are reviewed and evaluated. The models reviewed are the progressive ratio, choice, extinction, conditioned reinforcement and second-order schedule paradigms. These animal models are evaluated according to two criteria that are established herein as necessary and sufficient criteria for the evaluation of animal models of human psychopathology: reliability and predictive validity. The development of animal models of drug craving will have heuristic value and allow a systematic investigation of the neurobiological mechanisms of craving.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244907
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  • 6
    Electronic Resource
    Electronic Resource
    The effects of cocaine on operant responding for food in several strains of mice (1997)
    Springer
    Psychopharmacology 132 (1997), S. 202-208 
    Details
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Operant behavior ; Genetics ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The availability of numerous genetically homogenous mouse strains permits the analysis of genetic influences on behavior and also behavioral sensitivity (responsivity) to drugs of abuse. The current study was conducted to characterize discriminated operant responding for food in four inbred strains (Balb/cByJ, DBA/2J, C57BL/6J, SJL/J), an F1 Hybrid (C57BL/6×SJL), and one outbred strain (CD1) of mouse. The effect of cocaine on this operant behavior was also examined. Initially, all animals were trained to nosepoke for food on a continuous reinforcement schedule. The minimum response requirement for reinforcement was increased every 5 days until the animals were responding on an FR-15 schedule of reinforcement. All strains increased operant responding as the schedule of reinforcement was raised. However, significant differences in response rate and discrimination learning were observed among the various strains of mice. Cocaine administration reduced operant responding for food in Balb/cByJ, C57BL/6J, C57BL/6×SJL/J and CD1 mice at a dose of 15.0 mg/kg, whereas higher doses were required in DBA/2J mice (30.0 mg/kg) and SJL/J mice (56.0 mg/kg). These results suggest that operant performance and the effect of cocaine on this behavior is differentially influenced by genetic make-up.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050337
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  • 7
    Electronic Resource
    Electronic Resource
    Hierarchical strategy for phenotypic analysis in mice (1999)
    Springer
    Psychopharmacology 147 (1999), S. 2-4 
    Details
    ISSN: 1432-2072
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130051127
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  • 8
    Electronic Resource
    Electronic Resource
    Amphetamine derivatives induce locomotor hyperactivity by acting as indirect serotonin agonists (1991)
    Springer
    Psychopharmacology 104 (1991), S. 293-301 
    Details
    ISSN: 1432-2072
    Keywords: Amphetamine ; Methyenedioxyamphetamine ; Methylenedioxymethamphetamine ; MBDB ; p-Chloroamphetamine ; Fluoxetine ; Locomotion ; Serotonin ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Derivatives of amphetamine are potent releasers of both dopamine (DA) and serotonin (5-HT), but the relative contributions of DA and 5-HT release to the behavioral effects of these drugs have not been established. Previously, S-(+)3,4-methylendioxymethamphetamine (S-(+)MDMA) was found to produce locomotor hyperactivity in rats which was dependent on 5-HT release. The present study found that MBDB (1.25, 2.5, 5.0 or 10.0 mg/kg), the alpha-ethyl derivative of MDMA that produces little or no direct DA release, also induced locomotor hyperactivity that lasted for greater than 60 min after the 5.0 and 10.0 mg/kg doses. MBDB produced spatial patterns of locomotor hyperactivity and suppression of exploratory activity (holepokes and rearings) very similar to the behavioral syndrome produced by MDMA. MBDB-induced hyperactivity was blocked by pretreatment with the selective 5-HT uptake inhibitor fluoxetine (2.5 or 10 mg/kg), suggesting that MBDB produced behavioral effects via uptake-carrier mediated release of 5-HT. Similarly, fluoxetine pretreatment blocked the locomotor hyperactivity produced byS-(+)3,4-methylenedioxyamphetamine (3.0 mg/kg) orp-chloroamphetamine (2.5 mg/kg), supporting a serotonergic basis for the action of these drugs. Tissue levels of 5-HT and its metabolite 5-HIAA were decreased 40 min after administration ofS-(+)MDMA (3.0 mg/kg) or MBDB (5.0 mg/kg), and these decreases were prevented by fluoxetine pretreatment.S-(+)MDMA also produced a fluoxetine-sensitive increase of tissue DA levels, suggesting that 5-HT release may indirectly result in increased DA release, although MBDB did not significantly increase DA levels. These results point to a central role for 5-HT release in the stimulant-like behavioral effects of substituted derivatives of amphetamine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246026
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  • 9
    Electronic Resource
    Electronic Resource
    d-Amphetamine in squirrel monkeys of different social status: Effects on social and agonistic behavior, locomotion, and stereotypies (1983)
    Springer
    Psychopharmacology 81 (1983), S. 183-190 
    Details
    ISSN: 1432-2072
    Keywords: Amphetamine ; Social behavior ; Motor activities ; Squirrel monkeys ; Dominance ; Stereotypies ; Sex differences ; Age ; Agonistic behavior
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influences of social status on amphetamine-induced behavioral effects in squirrel monkeys were investigated. Social status was determined by constructing a sociogram. d-Amphetamine (0.3–1.0 mg/kg orally, 0.3 and 0.6 mg/kg IM) increased stereotyped head movements and reduced the time spent in the sitting posture in all monkeys (N=25) regardless of sex, age, or social status. The high levels of locomotor activity in dominant and juvenile monkeys were decreased at higher amphetamine doses (0.6 mg/kg IM, 0.6 and 1.0 mg/kg orally), whereas the same doses increased locomotion in otherwise less active subdominant and submissive animals. Low doses of amphetamine (0.1, 0.3 mg/kg) decreased the incidence of agonistic behavior initiated by dominant monkeys, and higher doses (0.6, 1.0 mg/kg) caused these monkeys to change from predominant initiators of agonistic behavior into recipients. At 2 h after amphetamine administration (0.3 mg/kg IM), the high levels of locomotor behavior had returned to baseline, the social isolation began to disappear, and the disrupted agonistic behavior of dominant monkeys returned to control levels, yet the stereotyped head movements continued to occur with high frequency. In half of the monkeys, amphetamine produced a large increase in distress-like vocalizations. Amphetamine-mediated motor stereotypies may be mediated by mechanisms different than those responsible for agonistic behavior. The selective changes in agonistic behavior by dominant monkeys when challenged with amphetamine may reflect a status-related functional alteration of catecholaminergic processes upon which the drug acts.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427259
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  • 10
    Electronic Resource
    Electronic Resource
    Effects of buspirone and gepirone on IV cocaine self-administration in rhesus monkeys (1992)
    Springer
    Psychopharmacology 108 (1992), S. 289-294 
    Details
    ISSN: 1432-2072
    Keywords: Cocaine abuse ; Buspirone ; Gepirone ; Chlorpromazine ; Self-administration of drugs ; Dopamine antagonists ; Rhesus monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Buspirone and gepirone were evaluated as potential pharmacotherapies for cocaine abuse by studying the effects of acute and repeated treatment on IV cocaine self-administration in rhesus monkeys. Chlorpromazine was also evaluated as a positive control. Effects of IV drug pretreatments were tested during daily 60-min sessions with lever-pressing reinforced under a fixed-ratio 10 schedule of 0.02 or 0.05 mg/kg cocaine infusions. Acute pretreatment with buspirone (0.1 and 0.3 mg/kg, IV) increased rates of cocaine self-administration without disrupting food pellet consumption. Some doses of buspirone also produced changes in rates of cocaine self-administration without altering the within-session pattern of responding. In contrast, acute doses of gepirone had little effect on rates of cocaine self-administration, while disruptions in food consumption and changes in the within-session pattern of cocaine self-administration were obtained at the highest dose of gepirone tested (1.0 mg/kg). When either buspirone (0.1 and 0.3 mg/kg, IV) or gepirone (0.1 mg/kg, IV) were administered daily for 10 days, consistent effects on cocaine self-administration were not observed. Thus, the effects of acute buspirone administration on cocaine-maintained behavior were similar to the effects produced by chlorpromazine and other dopaminergic antagonists, whereas, gepirone was ineffective. These results provide some support for further evaluation of buspirone as a potential pharmacotherapy for cocaine abuse, although its lack of efficacy with repeated treatment is not encouraging. The negative results with gepirone provide less rationale for continued investigations with this drug, possibly because of its lesser involvement than buspirone with dopaminergic neurotransmission.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245114
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