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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 79 (1983), S. 29-31 
    ISSN: 1432-2072
    Keywords: Heroin self-administration ; Reinstatement ; Priming ; Relapse of drug-taking behavior
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Non-contingent, ‘priming’ IV drug injections led to reinstatement of heroin-reinforced responding after a period of extinction. Rats implanted with IV catheters were trained to self-administer heroin (100 μg/kg/infusion diacetylmorphine HCl) and were given test sessions consisting of a period of self-administration followed by extinction conditions. ‘Priming’ infusions of heroin and other drugs were presented during extinction and lever pressing following the injection was observed. Priming injections of 50, 100 and 200 μg/kg heroin effectively restored responding after a period of extinction. Morphine and, to a lesser extent, amphetamine and apomorphine also reinstated heroin-reinforced responding whereas cocaine and clonidine did not. These results may help our understanding of ‘relapse of drug-taking’ behavior.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Key words Acamprosate ; Dopamine ; Heroin self-administration ; Nucleus accumbens ; Reinstatement ; Relapse ; Sensitization ; Stress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Acamprosate (calcium-acetyl homotaurinate) is a new compound used in the treatment of alcohol abuse. Because of the putative link between alcoholism and the endogenous opioid systems in both humans and laboratory animals, we tested in rats the effects of acamprosate on behavioral and neurochemical effects of opioid drugs related to their abuse potential. These included sensitization to the behavioral effects of morphine, morphine-induced dopamine (DA) release in the nucleus accumbens (NAS), intravenous (IV) heroin self-administration and relapse to heroin seeking in drug-free rats. In experiment 1, rats were injected daily with either morphine (10 mg/kg, SC) or saline for 14 days. Three days later in a test for the expression of sensitization, an injection of morphine (10 mg/kg) resulted in increased locomotor activity and enhanced DA release in the NAS in rats previously exposed to morphine. Acamprosate (two injections of 200 mg/kg; 12 h apart; IP) suppressed the expression of the sensitized responses, but did not alter the effects of morphine in drug-naive control rats. In experiment 2, it was found that acamprosate (two injections of 50–200 mg/ kg; IP) had no consistent effects on IV heroin self-administration (50–100 μg/kg per infusion) and, in experiment 3, that acamprosate (100–200 mg/ kg, IP) did not alter reinstatement of drug seeking induced by priming injections of heroin (0.25 mg/kg, SC) or a footshock stressor (15 min; 0.5 mA) after a 5- to 8-day period of extinction. Thus, although acamprosate attenuated the expression of sensitized locomotor activity and DA release in the NAS, it did not have any consistent effect on either the intake of heroin during the maintenance phase or the relapse to heroin seeking in a drug-free state. Thus, to the extent that the self-administration and the reinstatement procedures provide valid preclinical models for drug use and relapse in humans, our data suggest that acamprosate may not be effective in altering drug-taking behavior in heroin users.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Corticotropin-releasing factor ; CRF receptor ; Drug self-administration ; Heroin ; Reinstatement ; Relapse ; Stress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have found that peptide antagonists of corticotropin-releasing factor (CRF) receptors attenuate reinstatement of heroin and cocaine seeking induced by footshock. Here we examined the effect of a non-peptide, selective CRF1 receptor antagonist, CP-154,526, on reinstatement of heroin and cocaine seeking induced by footshock. Rats were trained to self-administer heroin or cocaine (0.1 and 1.0 mg/kg per infusion, IV, respectively) for 9–12 days. Extinction sessions were given for up to 14 days, during which saline was substituted for the drugs. Tests for reinstatement were then conducted after exposure to intermittent footshock (10 or 15 min, 0.5 mA). The footshock stressor reliably reinstated extinguished cocaine- and heroin-taking behavior. Pretreatment with CP-154,526 (15 and 30 mg/kg, SC) significantly attenuated the reinstatement effect of the stressor in both heroin- and cocaine-trained rats. CP-154,526, administered in the absence of the footshock stressor, did not affect extinguished drug seeking. In addition, in a separate experiment, CP-154,526 was shown not to alter high rates of lever pressing for a 10% sucrose solution, suggesting that the suppression of lever pressing in stress-induced reinstatement is not caused by a performance deficit. These results extend previous reports on the role of CRF in reinstatement of drug seeking induced by stressors. The present data also suggest that, to the extent that exposure to environmental stressors provoke relapse to drug use in humans, systemically effective CRF receptor antagonists may be of use in the treatment of relapse to drug use.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 114 (1994), S. 523-527 
    ISSN: 1432-2072
    Keywords: Heroin ; Intravenous drug self-administration ; Opioid drugs ; Progressive ratio ; Stress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of a mild footshock on intravenous heroin self-administration was examined in male rats. Animals in the stress condition were exposed to 10 min of intermittent footshock (0.5 mA; 0.5 s on, with a mean off period of 40 s) before each of four daily self-administration sessions. Animals in the control group were not exposed to footshock. Following acquisition of heroin-reinforced behavior (100 µg/kg per infusion), during which no group differences emerged, animals were placed on a progressive ratio schedule of reinforcement and were subsequently tested under a decreasing series of doses. Animals exposed to footshock before each drug session had higher rates of lever pressing for heroin and achieved higher final ratios on the progressive ratio schedule than animals in the control group at the higher doses of heroin. Thus, under the conditions of this experiment, exposture to mild intermittent stress appeared to enhance the reinforcing efficacy of heroin. The parameters of footshock used in the present study, and its relation to drug availability may characterize conditions under which stress leads to increased opioid abuse.
    Type of Medium: Electronic Resource
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