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  • 1
    Electronic Resource
    Electronic Resource
    Fixed-interval schedules for drug self-administration in the rat (1989)
    Springer
    Psychopharmacology 99 (1989), S. 136-139 
    Details
    ISSN: 1432-2072
    Keywords: Fixed-interval ; Self-administration ; Second-order schedule ; Heroin ; Cocaine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The practicality of using second-order fixed-interval schedules in studies of heroin reinforcement with rats was examined. Optimum rates of responding were obtained with a dose of 0.03 mg/kg/infusion and an interval duration of 3 min. In addition, schedules consisting of a only a single interval were shown to be practical, leading to response rates comparable to those obtained with cocaine or food as reinforcer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00634468
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  • 2
    Electronic Resource
    Electronic Resource
    Nicotine maintains robust self-administration in rats on a limited-access schedule (1989)
    Springer
    Psychopharmacology 99 (1989), S. 473-478 
    Details
    ISSN: 1432-2072
    Keywords: Nicotine ; Self-administration ; Reinforcement ; Mecamylamine ; Hexamethonium ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intravenous nicotine maintained substantial responding on the drug-reinforced lever with a limited-access, fixed-ratio 5 schedule of self-administration. Responding demonstrated the expected pharmacological sensitivity; it was dose-dependently reduced by pre-session treatment with either nicotine or mecamylamine but not with hexamethonium. In addition, responding was dependent on the size of the unit dose, with maximum values occurring at 0.01 and 0.03 mg/kg/infusion. Self-administration behavior decreased at doses both above and below these, and extinction followed the substitution of saline for nicotine. Total session drug intake increased with unit dose up to a maximal value of approximately 0.5 mg/kg at 0.03 mg/kg/infusion, but did not increase further at the 0.06 mg/kg/infusion dose. A decrease in the time-out duration at the dose of 0.03 mg/kg/infusion also did not change the total session intake of nicotine. It is suggested that nicotine intake is controlled both by the total amount of drug obtained and by the magnitude of the unit dose. These results demonstrate that intravenous nicotine can maintain substantial self-administration behavior in rodents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00589894
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  • 3
    Electronic Resource
    Electronic Resource
    Evidence for opioid mechanisms in the behavioral effects of nicotine (1988)
    Springer
    Psychopharmacology 96 (1988), S. 29-35 
    Details
    ISSN: 1432-2072
    Keywords: Nicotine ; Opioid-nicotine interactions ; Naltrexone ; Fixed-interval responding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of nicotine, heroin, mecamylamine, and naltrexone were studied in rats trained to respond under a fixed-interval 3-min schedule of food presentation. Nicotine (0.1–3.0 mg/kg) first increased, then decreased response rates; heroin (0.03–0.6 mg/kg) produced only dose-related response rate decreases. Mecamylamine (0.1–3.0 mg/kg) and naltrexone (0.3–10.0 mg/kg), administered alone, each had little effect on response rates. However, when administered in combination with increasing doses of nicotine, mecamylamine (1.0 mg/kg) blocked the increases in response rate caused by 0.3 and 1.0 mg/kg nicotine and partially reversed the decreases in rate caused by 3.0 mg/kg nicotine. In contrast, the combination of naltrexone and nicotine, at doses of each that alone either had no effect or increased response rates, markedly decreased responding. This phenomenon was not evident during the first pairing of naltrexone and nicotine, but appeared in the second and subsequent pairings. After drug combinations had been tested, the nicotine dose-response curve was unchanged from its previous values, and naltrexone alone produced no tendency to decrease response rate. These observations may be related to previous results that have suggested a role for endogenous opioids in mediating certain of the behavioral effects of nicotine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02431529
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  • 4
    Electronic Resource
    Electronic Resource
    The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine (1992)
    Springer
    Psychopharmacology 107 (1992), S. 285-289 
    Details
    ISSN: 1432-2072
    Keywords: Nicotine ; Mesolimbic dopamine ; Reinforcement ; Nucleus accumbens ; Dopamine ; 6-Hydroxydopamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to self-administer nicotine on a fixed-ratio schedule of reinforcement. Infusion of the nicotinic antagonist chlorisondamine into the cerebral ventricles produced a sustained reduction in nicotine self-administration compared to vehicle-treated controls. Lesions of the mesolimbic dopamine system were produced by microinfusion of 6-hydroxydopamine into the nucleus accumbens. Following production of the lesions, nicotine self-administration was markedly reduced for the 3-week test period; motor impairment did not appear to be responsible. Post mortem analysis of brain tissue showed that the lesion produced a pronounced decrease in dopamine content of the nucleus accumbens and the olfactory tubercle, and a small depletion in the striatum. These data demonstrate that the reinforcing effects of nicotine occur within the central nervous system, and that the mesolimbic dopamine projection plays an important role in these effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245149
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  • 5
    Electronic Resource
    Electronic Resource
    The mu opioid agonist DAMGO alters the intravenous self-administration of cocaine in rats: mechanisms in the ventral tegmental area (1999)
    Springer
    Psychopharmacology 141 (1999), S. 428-435 
    Details
    ISSN: 1432-2072
    Keywords: Key words Cocaine reinforcement ; Ventral tegmental area ; Mu opioid ; Kappa opioid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Microinfusions of the opioid subtype-selective agonist DAMGO and antagonist CTOP into the ventral tegmental area (VTA) were used to examine the role of mu opioid receptors in this area of the mesolimbic dopamine system in regulating cocaine reinforcement. Long-Evans rats were trained to self-administer cocaine intravenously and prepared with intracranial cannulae directed to the VTA. At doses of cocaine on the descending limb of the cocaine dose-response curve, the mu-selective agonist DAMGO produced a dose-related decrease in cocaine self-administration when delivered by microinfusion into the VTA. At a dose of cocaine on the ascending limb of the self-administration dose-response curve, DAMGO microinfusions produced an increase in responding for the drug. The mu-selective antagonist CTOP produced small effects on cocaine self-administration. A kappa-selective agonist and antagonist (U50,488 and norbinaltorphimine, respectively) produced either no effects or small effects that did not show consistent trends with dose. These experiments suggest that the mu agonist DAMGO is able to shift the dose-response curve for cocaine self-administration to the left. This effect appears to be specific for mu as compared to kappa agonists. These data are consistent with the known differential distribution of opioid receptor subtypes within the VTA, and with the effects of opioid compounds in the VTA on dopamine release in the mesolimbic synaptic field. The data show that a mu opioid mechanism in the somatodendritic region can alter reinforcement processes for cocaine, which acts predominantly at the terminal field of dopamine cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050853
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  • 6
    Electronic Resource
    Electronic Resource
    Selective dopamine antagonists reduce nicotine self-administration (1991)
    Springer
    Psychopharmacology 104 (1991), S. 171-176 
    Details
    ISSN: 1432-2072
    Keywords: Nicotine self-administration ; Locomotor activity ; Dopamine antagonists ; SCH23390 ; Spiperone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of selective D1 (SCH23390) and D2 (spiperone) dopamine antagonists, as well as of haloperidol, were examined on nicotine self-administration, food-maintained responding, and locomotor activity in rats. Antagonists reduced both operant responding and locomotor activity. Response patterns indicated that motor impairment was not the cause of the decreases, since responding was attenuated only in the latter half of operant sessions. Locomotor activity scores were significantly reduced by SCH23390, but not by spiperone. The effects of dopamine antagonists on nicotine self-administration are different from the effects of these antagonists on cocaine self-administration. Results are discussed in terms of the role of dopamine in drug reinforcement versus its role in sensorimotor integration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244174
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  • 7
    Electronic Resource
    Electronic Resource
    Opiate antagonists reduce cocaine but not nicotine self-administration (1991)
    Springer
    Psychopharmacology 104 (1991), S. 167-170 
    Details
    ISSN: 1432-2072
    Keywords: Cocaine ; Nicotine ; Self-administration ; Naltrexone ; Naloxone ; Reinforcement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained to self-administer cocaine in 1-h sessions on a fixed ratio 5 (FR5) schedule of reinforcement. Acquisition was carried out at a unit dose of 0.3 mg/kg and responding was then stabilized at cocaine doses of 0.1, 0.3, and 1.0 mg/kg/infusion. Pretreatments with naltrexone (0.1–10 mg/kg, SC) 20 min prior to the start of self-administration sessions resulted in decreases in cocaine self-administration at doses of 0.1 and 0.3 mg/kg/infusion, but not at 1.0 mg/kg/infusion. Decreases depended on the dose of naltrexone used, with greater decreases in self-administration occurring at higher antagonist doses. In addition, treatment with the opiate antagonist naloxone also reduced cocaine self-administration at a unit dose of 0.3 mg/kg. A group of rats trained to self-administer nicotine at a dose of 0.03 mg/kg/infusion on the same schedule of reinforcement was unaffected by naltrexone treatment. These results may indicate that an endogenous opiate system plays a role in cocaine reinforcement.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244173
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  • 8
    Electronic Resource
    Electronic Resource
    Manipulations of mu-opioid and nicotinic cholinergic receptors in the pontine tegmental region alter cocaine self-administration in rats (1999)
    Springer
    Psychopharmacology 145 (1999), S. 412-417 
    Details
    ISSN: 1432-2072
    Keywords: Key words Drug reinforcement ; Cocaine self-administration ; Pedunculopontine tegmental nucleus ; Mu opioid ; Nicotinic cholinergic mechanisms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The pedunculopontine tegmental nucleus (PPTg) has been implicated in drug reward, particularly in the development of dependence. However, little is known of the receptor systems within this nucleus which might be involved. Furthermore, some research suggests that the PPTg may also be part of the neuronal circuitry involved in established drug-taking behavior. Objective: The objective of these experiments was to examine the role of mu-opioid and nicotinic cholinergic mechanisms in the PPTg in cocaine self-administration. Methods: Microinfusions of mu-opioid and nicotinic receptor selective compounds were made into the PPTg of rats trained to self-administer cocaine intravenously, in the vicinity of cholinergic cells which are known to project to the midbrain dopamine neurons of the ventral tegmental area (VTA). Results: The mu-opioid selective agonist DAMGO, tested at doses of 0, 0.05 and 0.5 µg, produced a dose-related reduction in the number of cocaine infusions obtained during the 1-h self-administration sessions. The mu-selective antagonist CTOP (0–2 µg) and nicotine (0–10 µg) did not produce significant changes in cocaine self-administration. Microinfusions of the nicotinic antagonist dihydro-β-erythroidine (0–30 µg) produced a small but significant increase in cocaine-maintained responding. Conclusions: These data show that mu-opioid mechanisms in the PPTg can influence cocaine self-administration markedly. Moreover, the data demonstrate that PPTg circuitry can influence drug reward in already-established drug-reinforced behavior, as well as during the development of dependence (as shown by previous research).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130051075
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