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  • 1
    Electronic Resource
    Electronic Resource
    Nicotine self-administration in rats: strain and nicotine pre-exposure effects on acquisition (1997)
    Springer
    Psychopharmacology 129 (1997), S. 35-43 
    Details
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Reinforcement ; Intravenous self-administration ; Strain differences ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Nicotine has been shown to maintain intravenous self-administration behaviour in humans and laboratory animals. However, factors critical in the initiation of nicotine self administration are not well defined. In particular genetic differences and effects of pre-exposure to nicotine have not been examined. Male Sprague-Dawley or Long-Evans rats were surgically prepared with indwelling jugular catheters and 3 days later received chronic injections of nicotine (0.4 mg/kg SC) or vehicle (saline, 1 ml/kg) for 7 days in their home cage. The next day, 2-h daily test sessions were initiated, during which rats were given the opportunity to nose-poke for nicotine infusions (0.015, 0.03 or 0.06 mg/kg per infusion) under a one-response fixed-ratio (FR-1) schedule of reinforcement with a 20-s time out after each infusion. One hole was defined as active while pokes in the other hole were recorded but had no scheduled consequence. The response requirement was increased progressively to five (FR-5) over successive sessions. Both saline- and nicotine-pretreated Sprague-Dawley rats showed a preference for the active hole, while only the saline-pretreated Long-Evans rats acquired the self-administration as defined by significant differences between responding in the active versus the inactive holes. The Fisher (F344) and Lewis inbred strains also failed to acquire self-administration of nicotine under these conditions. With Sprague-Dawley and Long-Evans rats that acquired the self-administration, and showed stable levels of maintained responding for nicotine, substituting saline for the nicotine or pretreating with mecamylamine (2.0 mg/kg SC) extinguished the behaviour. When dose per infusion was varied, an inverted U-shaped dose-response curve was obtained. These results support previous reports that nicotine can serve as a reinforcer in rodents and demonstrate that environmental factors such as prior nicotine exposure or genetic factors such as rat strain can affect acquisition of nicotine self-administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050159
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  • 2
    Electronic Resource
    Electronic Resource
    Behavioural and neurochemical characteristics of phentermine and fenfluramine administered separately and as a mixture in rats (1997)
    Springer
    Psychopharmacology 131 (1997), S. 296-306 
    Details
    ISSN: 1432-2072
    Keywords: Key words Drug discrimination ; Microdialysis ; Dopamine ; Serotonin ; Phentermine ; Fenfluramine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clinical case studies suggest that combined administration of the serotonergic agent fenfluramine (FEN) and the weak amphetamine-like anorexic agent phentermine (PHEN) may be useful in the treatment of alcohol and cocaine addictions. The present experiment examined the nature of the interaction between the two agonists using the drug discrimination paradigm. In vivo microdialysis served to examine the neurochemical profile of dopamine and serotonin release in the nucleus accumbens. In conscious rats, acute injections of FEN (1.0–2.0 mg/kg IP) or PHEN (1.0–2.0 mg/kg IP) selectively elevated levels of serotonin and dopamine in the nucleus accumbens, respectively. A mixture (1 mg/kg of each) increased levels of both amines by similar magnitudes to those observed with each individually. Three groups of Sprague-Dawley rats were trained to discriminate (1) FEN (1.0 mg/kg IP) alone, (2) PHEN (1.0 mg/kg IP) alone or a mixture (3) PHEN+FEN (1 mg/kg of each, IP) from saline under a fixed ratio (FR-10) schedule of food reinforcement. Rats acquired the mixture discrimination rapidly, while for the other groups the training dose had to be increased to 2.0 mg/kg to attain stimulus control. The individual components of the mixture at the training dose generalized partially to the mixture, and complete generalisation was observed following 3.0 mg/kg FEN or PHEN. Rats trained to discriminate the individual components showed respective cross-generalisation profiles. Generalisation to cocaine (0.3–10.0 mg/kg IP), amphetamine (0.1–3.0 mg/kg IP) and nicotine (0.1–0.8 mg/kg SC) was greatest in the MIX-trained rats, while partial or no generalisation was observed in rats trained to discriminate the individual compounds. From the present results, it may be concluded that the two drugs given as a mixture do not produce a novel cue. Rather, these aminergics appear to interact additively. Furthermore, the dual stimulation of the amines by the mixture may be the basis for the cueing effects of the FEN+PHEN drug mixture, and its effectiveness in treating drug addictions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050296
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Behavioural and biochemical adaptations to nicotine in rats: influence of MK801, an NMDA receptor antagonist (1997)
    Springer
    Psychopharmacology 134 (1997), S. 121-130 
    Details
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Rats ; MK801 ; NMDA receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic exposure of rats to nicotine can result in sensitization to the stimulant effects of nicotine on locomotor activity. At a biochemical level, chronic exposure to nicotine increases the number of CNS nicotinic binding sites, and this has been suggested as the basis for sensitization to nicotine. The present experiment was conducted to examine the effects of MK801, an NMDA receptor antagonist, on sensitization to nicotine. In addition, the hypothesis that MK801 may block behavioural sensitization by preventing the up-regulation of nicotinic receptors was tested by measuring receptor numbers in the same individuals using quantitative autoradiography with [3H]-cytisine and [3H]-MK801. Male Sprague-Dawley rats were chronically treated with nicotine (0.4 mg/kg SC) or saline daily for 7 days. Over the next 2 days, in a counterbalanced order, rats were challenged with nicotine (0.4 mg/kg SC) or saline and locomotor activity was monitored. In saline-pretreated rats, nicotine produced a small increase in activity. Nicotine-pretreated rats exhibited higher levels of activity following a nicotine challenge. This sensitized response was attenuated in rats administered MK801 (0.3 mg/kg IP) 30 min before each daily nicotine injection. Rats pretreated with MK801 alone showed activity scores no different from saline pretreated control groups. Biochemical studies revealed increased [3H]-cytisine binding following chronic nicotine treatment; however, receptor increases were significantly attenuated by MK801 pretreatment. Binding of [3H]-MK801 remained unchanged across the four groups. The results suggest that MK801 prevents behavioural sensitization to nicotine via the prevention of receptor up-regulation. Although the findings support the notion that receptor up-regulation may be the basis for the increased responsiveness to nicotine, other interpretations are possible.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050433
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    Paper (German National Licenses)
    Fulltext
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