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  • Cocaine  (11)
  • Dependence  (2)
  • Elevated plus-maze  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Heroin and cocaine intravenous self-administration in rats: Mediation by separate neural systems (1982)
    Springer
    Psychopharmacology 78 (1982), S. 204-209 
    Details
    ISSN: 1432-2072
    Keywords: Cocaine ; Heroin ; Opiate ; Dopamine ; Alpha flupenthixol ; Psychomotor-stimulant ; Natrexone ; Receptor antagonists ; Self-administration ; Reinforcement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The hypothesis that separate neural systems mediate the reinforcing properties of opiate and psychomotor stimulant drugs was tested in rats trained to lever-press for IV injections of either cocaine or heroin during daily 3-h sessions. Pretreatment with the opiate receptor antagonist drug naltrexone produced dose-dependent increases in heroin self-administration, but had no effect on the rate or pattern of cocaine self-administration. Similarly, pretreatment with low doses of the dopamine antagonist drug alpha-flupenthixol produced dose-dependent increases in cocaine but not heroin self-administration. High doses of alpha-flupenthixol eliminated all responding for cocaine and slightly reduced heroin self-administration. The specificity with which the two antagonist drugs exerted their behavioral effects strongly suggests that independent neural substrates are responsible for the reinforcing actions of heroind and cocaine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428151
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  • 2
    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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  • 3
    Electronic Resource
    Electronic Resource
    Cocaine antagonizes anxiolytic effects of ethanol (1984)
    Springer
    Psychopharmacology 84 (1984), S. 28-31 
    Details
    ISSN: 1432-2072
    Keywords: Cocaine ; Ethanol ; Anxiety ; Ataxia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A Geller-Seifter paradigm for discerning anxiolytic and ataxic effects of drugs was used to study the interactions between low doses of ethanol and cocaine. Ethanol produced significant anxiolytic and ataxic effects at a dose of 1 g/kg. Cocaine at a dose as low as 10 mg/kg markedly antagonized the anxiolytic effect of ethanol, but simultaneously augmented ethanol's ataxic effects, as measured by response rates during a random-interval schedule. These results indicate that ethanol may interact to a significant degree with brain aminergic systems and that, contrary to popular dogma, stimulants may reverse some components of ethanol intoxication, but increase ethanol's debilitating motor effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432019
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  • 4
    Electronic Resource
    Electronic Resource
    Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin self-administration in rats (1984)
    Springer
    Psychopharmacology 84 (1984), S. 167-173 
    Details
    ISSN: 1432-2072
    Keywords: Cocaine ; Heroin ; Self-administration ; Opiate ; Psychomotor stimulant ; Dopamine ; Nucleus accumbens ; 6-Hydroxydopamine ; Reinforcement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The hypothesis that separate neural systems mediate the reinforcing properties of opioid and psychomotor stimulant drugs was tested by examining the role of mesolimbic dopamine (DA) neurons in maintaining intravenous heroin and cocaine self-administration. After local destruction of the DA terminals in the nucleus accumbens (NAcc) with 6-hydroxydopamine (6-OHDA), rats trained to self-administer cocaine and heroin on alternate days were observed for changes in their drug-seeking behaviors. Postlesion responding for cocaine showed a time-dependent decrease or extinction, whereas heroin self-administration showed a time-dependent recovery. By the fifth trial postlesion, heroin self-administration had recovered to 76% of prelesion baseline levels, but cocaine self-administration had dropped to 30% of prelesion baseline rates. Thus, selective lesions of the DA terminals in the nucleus accumbens significantly attenuate cocaine but not heroin self-administration. These data support the hypothesis that independent neural subtrates are responsible for the reinforcing actions of these two drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00427441
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  • 5
    Electronic Resource
    Electronic Resource
    Desmethylimipramine attenuates cocaine withdrawal in rats (1992)
    Springer
    Psychopharmacology 109 (1992), S. 305-314 
    Details
    ISSN: 1432-2072
    Keywords: Intracranial self-stimulation ; Brain stimulation reward ; Thresholds ; Self-administration ; Cocaine ; Stimulants ; Anhedonia ; Depression ; Withdrawal ; DMI ; Desipramine ; Desmethylimipramine ; Tricyclic antidepressants ; Drug abuse ; Beta-adrenergic receptors ; Downregulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Depression and anhedonia are two major symptoms of cocaine withdrawal in humans. Hence, pharmacological treatments effective in depression might also alleviate the symptoms of cocaine withdrawal. In the present study, the effects of acute and repeated administration of a tricyclic antidepressant, desmethylimipramine (DMI), were investigated in naive and cocaine-withdrawing rats. An animal model of cocaine withdrawal was used that employs the elevation in intracranial self-stimulation (ICSS) thresholds following the termination of prolonged periods of cocaine self-administration as a measure of an animal's “anhedonic” state. The influence of chronic DMI treatment onβ-adrenergic receptor binding and affinity was also correlated with the behavioral signs of cocaine withdrawal. Neither acute nor repeated DMI treatment influenced reward functions in rats that were not undergoing cocaine withdrawal. However, repeated DMI treatment significantly down-regulatedβ-adrenergic receptors, and shortened the duration of the post-cocaine “anhedonia” (elevation in thresholds). Furthermore, the magnitude of theβ-adrenergic receptor down-regulation correlated significantly with the degree of effectiveness of DMI treatment in reversing the post-cocaine “anhedonia”. However, chronic DMI treatment did reduce the amount of cocaine self-administered by the animals. The reversal of the post-cocaine anhedonia in this animal model of cocaine withdrawal by chronic DMI treatment demonstrates the potential usefulness of the model in identifying new pharmacotherapies for cocaine withdrawal. In addition, the results indicate that tricyclic antidepressants may be able to ameliorate some of the symptoms of cocaine withdrawal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245878
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  • 6
    Electronic Resource
    Electronic Resource
    CRF antagonist reverses the “anxiogenic” response to ethanol withdrawal in the rat (1991)
    Springer
    Psychopharmacology 103 (1991), S. 227-232 
    Details
    ISSN: 1432-2072
    Keywords: Ethanol ; Withdrawal ; Anxiety ; Elevated plus-maze ; Corticotropin-releasing factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of the neuropeptide corticotropin-releasing factor (CRF) in mediating the behavioral effects of ethanol withdrawal in the rat was examined using the elevated plus-maze test. In Experiment 1, CRF (0.5 µg ICV) reduced the percentage of time spent on the open arms of the elevated plus-maze, consistent with an “anxiogenic-like” effect. CRF also reduced the total number of arm entries, indicating a reduction in general activity. Low doses (5 and 25 µg ICV) of the CRF antagonist, alpha-helical CRF produced no behavioral effects in the elevated plus-maze, while a higher dose (50 µg ICV) elicited CRF-like activity. In experiment 2, rats were maintained for 2–3 weeks on a liquid diet containing ethanol (8.5–11.5% v/v) or sucrose. Eight hours after withdrawal from the ethanol diet rats displayed “anxiogenic-like” responses as well as a reduction in general activity in the elevated plus-maze compared with rats withdrawn from control diet. Alpha-helical CRF significantly antagonized the “anxiogenic-like” effects of ethanol withdrawal in the plus-maze. General activity and physical signs of ethanol withdrawal such as tail stiffness, body tremor and ventromedial distal flexion were unaffected by alpha-helical CRF. Blood Alcohol Levels (BALs) determined immediately after removal of the ethanol diet showed no group differences in ethanol consumption. These results suggest that increased activity of central CRF systems may mediate the anxiogenic effects of ethanol withdrawal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244208
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  • 7
    Electronic Resource
    Electronic Resource
    SDZ 208-911, an amino-ergoline with partial dopamine agonist properties, dose dependently increases cocaine self-administration in the rat (1994)
    Springer
    Psychopharmacology 113 (1994), S. 518-520 
    Details
    ISSN: 1432-2072
    Keywords: Cocaine ; Dopamine agonist ; Dopamine ; Partial agonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Brain dopamine neurotransmission appears to be an important component of the neural pathways involved in the maintenance of intravenous (IV) cocaine self-administration in rats. The effects of a novel partial dopamine agonist, SDZ 208–911, on intravenous cocaine self-administration in rats was studied. SDZ 208–911 at a dose range of 0.025–1.6 mg/kg SC dose-dependently increased the number of lever presses and drug intake in rats exposed to limited (3-h) daily access to cocaine on a continuous reinforcement schedule (0.75 mg/kg per injection). This behavioral profile is similar to that observed following administration of dopamine antagonist drugs and has been hypothesized to reflect a compensatory increase in drug intake due to a reduction of the reinforcing efficacy of the drug, probably because of functional antagonism at the receptor site. These results suggest that dopamine partial agonists may act as functional dopamine antagonists in the face of pharmacologically induced activation of brain dopamine function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245232
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  • 8
    Electronic Resource
    Electronic Resource
    Cocaine-but not food-seeking behavior is reinstated by stress after extinction (1997)
    Springer
    Psychopharmacology 132 (1997), S. 289-295 
    Details
    ISSN: 1432-2072
    Keywords: Key words Drug self-administration ; Cocaine ; Extinction ; Reinstatement ; Drug-seeking ; Drug relapse ; Stress ; Footshock ; Internal state ; Context
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Reinstatement of drug-seeking behavior after extinction constitutes a potential animal model of relapse to drug abuse. In a typical reinstatement experiment, previously drug-trained rats undergo extinction during which responding is no longer followed by drug delivery. After significant extinction is observed, rats are then exposed to an event expected to reinstate drug-seeking behavior. Using this procedure, it has been recently reported that footshock stress leads to reinstatement of drug-seeking in heroin-trained, presently drug-free rats. The purpose of the present study was to assess the generality of this effect of stress. Here we report that 15 min of intermittent footshock (0.86 mA; 0.5 s on, with a mean off period of 40 s) reinstated selectively cocaine-seeking behavior after 14 extinction sessions (rats were previously trained on a FR1 TO 20 s to obtain cocaine at a dose of 0.25 mg/infusion). In contrast, under similar experimental conditions, the same stressor did not reinstate food-seeking in food-trained rats after seven extinction sessions (rats were previously trained on a FR1 TO 20 s to obtain six food pellets). Rather, when the basal level of responding was sufficiently high, footshock stress induced a significant suppression of the instrumental performance. These data are discussed in light of several behavioral mechanisms which may explain the specificity of stress in reinstating drug-seeking behavior and not food-seeking behavior.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050347
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  • 9
    Electronic Resource
    Electronic Resource
    Serotonin1B receptor stimulation enhances dopamine-mediated reinforcement (1996)
    Springer
    Psychopharmacology 128 (1996), S. 150-160 
    Details
    ISSN: 1432-2072
    Keywords: Key words 5-HT1B receptors ; GBR-12909 ; CGS-12066B ; Self-administration ; 8-OH-DPAT ; Cocaine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of 5-HT1B receptor stimulation on dopamine-mediated reinforcement in rats was investigated using intravenous self-administration of the selective dopamine uptake inhibitor GBR-12909 on an FR5 schedule of reinforcement. Pretreatment with the 5-HT1A/1B receptor agonist CGS-12066B (1–10 mg/kg, IP) dose-dependently reduced the self-administration of GBR-12909 (83 μg/injection) by increasing the interval between drug injections, consistent with a enhancement of the reinforcing effects of GBR-12909. Additionally, CGS-12066B pretreatment (3 mg/kg, IP) shifted the dose-effect function for GBR-12909 self-administration to the left. Pretreatment with the selective 5-HT1A receptor agonist 8-OH-DPAT (0.03– 1.0 mg/kg, SC) had no significant effect on GBR-12909 self-administration (83 μg/injection), indicating that the effect of CGS-12066B is not mediated by the 5-HT1A receptor. Finally, CGS-12066B pretreatment (1–10 mg/kg, IP) did not alter the self-administration of cocaine (0.03–0.5 mg/injection), suggesting that the simultaneous stimulation of multiple 5-HT receptor subtypes by the indirect 5-HT agonist properties of cocaine may mask the effect of 5-HT1B receptor stimulation on DA-mediated reinforcement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050120
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  • 10
    Electronic Resource
    Electronic Resource
    Opiate withdrawal signs precipitated by naloxone following a single exposure to morphine: potentiation with a second morphine exposure (1997)
    Springer
    Psychopharmacology 129 (1997), S. 56-65 
    Details
    ISSN: 1432-2072
    Keywords: Key words Opiates ; Morphine ; Dependence ; Acute dependence ; Withdrawal ; Abstinence ; Naloxone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent studies in humans with no prior history of opiate abuse indicated that naloxone-precipitated signs of opiate withdrawal could be observed after a single exposure to morphine, and that the severity of withdrawal was enhanced following a second morphine exposure 24 h later. The current study was conducted to establish a paradigm in rodents that resembled these conditions described in humans. To that end, naloxone-precipitated (0.03–3.0 mg/kg) suppression of operant response rates and somatic signs of withdrawal following single or repeated treatments with morphine (5.0 mg/kg) were assessed in previously opiate-naive rats. In one group of rats, naloxone was administered 4 h after both the first and second morphine pretreatment, while in a separate group of rats naloxone was administered 4h after the second morphine pretreatment only. A single morphine pretreatment significantly increased naloxone’s potency to suppress operant response rates, and resulted in the precipitation by naloxone of certain somatic signs of withdrawal. The effects of naloxone on both dependent measures (operant response rates and somatic signs) were potentiated following a second morphine pretreatment, regardless of whether naloxone was administered following both morphine exposures or only following the second morphine exposure. Thus, repeated morphine administration appears to be the critical factor underlying the progressive increase in antagonist potency, whereas prior experience with naloxone is not a necessary factor. The results provide additional support for the hypothesis that the development of dependence on opiates is a progressive phenomenon that may begin with a single dosing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050162
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