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  • 1
    Electronic Resource
    Electronic Resource
    Locomotor activity after nicotine infusions into the fourth ventricle of rats
    Amsterdam : Elsevier
    Pharmacology, Biochemistry and Behavior 48 (1994), S. 749-754 
    Details
    ISSN: 0091-3057
    Keywords: Fourth ventricle ; Locomotor activity ; Mecamylamine ; Nicotine ; Prostration
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/0091-3057(94)90342-5
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  • 2
    Electronic Resource
    Electronic Resource
    Strain differences in the rewarding and dopamine-releasing effects of morphine in rats (1995)
    Springer
    Psychopharmacology 117 (1995), S. 240-247 
    Details
    ISSN: 1432-2072
    Keywords: Microdialysis Conditioned place preference ; Morphine Locomotor activity ; Genetic differences ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Studies examining differential sensitivity to psychoactive drugs in mice suggest that genotype may play a critical role. Furthermore, an involvement of genotype in mediating individual differences in sensitivity to the rewarding effects of several drugs of abuse has also been postulated. The aim of this study was to examine the conditioned rewarding and dopamine-releasing effects of morphine in two outbred rat strains commonly used in addiction research. Additionally, the behavioural and neuroendocrine responses of these strains to the stress of novelty were also examined. Basal locomotor activity was higher in Wistar rats than Sprague-Dawley following exposure to a novel environment. In contrast, elevations in plasma corticosteroid levels following novelty exposure did not differ between the two strains. In a counterbalanced place preference conditioning procedure, increasing doses of morphine (1.0–10.0 mg/kg SC) produced significant conditioned place preferences (CPP) in both Wistar and Sprague-Dawley strains. However, Wistar rats required a significantly larger dose of morphine (5.0 mg/kg) to produce a significant CPP than the Sprague-Dawley rats. In the latter strain, CPP occurred with doses of 3.0 mg/kg and greater. In parallel microdialysis experiments, both strains showed significant dose-related increases in dopamine release in the nucleus accumbens following acute morphine challenge (1.0–10.0 mg/kg SC). Again in Wistar rats, a larger dose of morphine was necessary to produce a significant increase in comparison to Sprague-Dawley rats. These results show that genetically distinct rat strains can show differential sensitivity to opioids, more specifically to drug-seeking responses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245193
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  • 3
    Electronic Resource
    Electronic Resource
    Plasma nicotine and cotinine levels following intravenous nicotine self-administration in rats (1999)
    Springer
    Psychopharmacology 143 (1999), S. 318-321 
    Details
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Cotinine ; Self-administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: The route of nicotine administration between animal models and humans is very different and further investigation by determining levels of nicotine entering into the circulatory system is warranted. Objective: The present study addresses the validity of the rat self-administration procedure by comparing plasma levels of nicotine in the rat with levels reported in smokers following cigarette consumption. Methods: Plasma levels of nicotine and its metabolite cotinine were measured in 17 rats following intravenous self-administration of a range of nicotine doses (0.015, 0.03 and 0.06 mg/kg per infusion). Results: The two larger unit doses supported reliable self-administration behaviour with no overall difference in the patterns of nicotine intake. However, the total nicotine intake over the 2-h session was related to unit dose and this correlated highly with nicotine and cotinine levels measured in blood collected from the tail vein. On average, cotinine levels (50–200 ng/ml) were approximately 2-fold higher than nicotine levels (40–120 ng/ml) in plasma. Following an extinction test for one session in which saline was substituted for nicotine, no change in behaviour was observed in the two groups, while plasma levels of nicotine and cotinine dropped to nominal levels. Conclusions: The concentrations of nicotine attained following nicotine self-administration appear to be similar to levels reported in smokers after cigarette consumption, providing further validation of this procedure as an animal model of nicotine dependence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050954
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  • 4
    Electronic Resource
    Electronic Resource
    Anxiety: a potential predictor of vulnerability to the initiation of ethanol self-administration in rats (1995)
    Springer
    Psychopharmacology 122 (1995), S. 369-373 
    Details
    ISSN: 1432-2072
    Keywords: Anxiety ; Elevated plus-maze ; Ethanol ; Oral self-administration ; Tension-reduction hypothesis ; Individual differences
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anxiolytic effects of ethanol have been proposed to be important factors in the initiation of ethanol consumption. To examine this hypothesis, drug-naive Wistar rats were tested in the elevated plusmaze to determine their initial level of anxiety. Based on their response, we separated the animals into anxious and non-anxious groups. After that, animals went through an oral ethanol self-administration procedure. Rats that were initially classified as anxious showed a significantly (P〈0.01) higher intake and preference for ethanol during the initiation phase of the voluntary drinking procedure than non-anxious animals. In another experiment, intraperitoneal (IP) injections of ethanol (0.5–1.5 g/kg) produced dose-dependent anxiolytic effects in rats when tested in the elevated plus-maze procedure. Blood ethanol levels following IP injections during the plus-maze test were similar to those reached during the oral ethanol self-administration procedure, which shows that the rats indeed drank sufficient amounts of ethanol to experience its anxiolytic effects. These findings indicate that the basal level of anxiety plays an important role in vulnerability to alcohol drinking.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246268
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  • 5
    Electronic Resource
    Electronic Resource
    Antagonism of stimulus properties of nicotine by dihydro-β-erythroidine (DHβE) in rats (2000)
    Springer
    Psychopharmacology 149 (2000), S. 140-146 
    Details
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Discrimination ; Taste aversion conditioning ; Antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Previous work has shown that a dose of DHβE, a competitive nicotinic receptor antagonist that blocked the discriminative stimulus properties of nicotine, was insufficient to block locomotor depression or operant rate-reducing effects of nicotine in rats. Examination of DHβE against other behavioural effects of nicotine may help in understanding its diverse actions. Objective: The present experiments examine the aversive stimulus properties of nicotine, a function implicated in the regulation of nicotine intake. Furthermore, to characterise the duration of pharmacological blockade produced by DHβE, the antagonist was examined in the drug discrimination (DD) procedure. Methods: Using the conditioned taste aversion (CTA) paradigm, male hooded rats were trained to avoid one of two distinctively flavoured solutions paired with nicotine (0.2 or 0.4 mg/kg) administration. In rats trained to discriminate 0.2 mg/kg SC nicotine in a two-lever procedure maintained under a tandem VI60”-FR10 schedule of food reinforcement, the offset of antagonism by DHβE was examined 5, 15 and 30 min following injection of nicotine (0.2 or 0.4 mg/kg SC) or vehicle. Results: Administration of DHβE (0.5, 1.6 and 5.0 mg/kg SC) 30 min before nicotine failed to block nicotine (0.4 mg/kg) CTA, while co-administration of DHβE (5.0 mg/kg SC) with nicotine (0.2 and 0.4 mg/kg SC) prevented the development of CTAs. This blockade complemented nicotine discrimination data in which DHβE blocked the discriminative stimulus effect of nicotine (0.2 or 0.4 mg/kg SC) for 45 min after its administration. Conclusions: These observations of DHβE’s short-lasting antagonism against the aversive and discriminative stimulus effects of nicotine support the involvement of the similar subtypes of nicotinic receptor in the mediation of these diverse behavioural effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002139900348
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  • 6
    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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  • 7
    Electronic Resource
    Electronic Resource
    Chronic caffeine exposure potentiates nicotine self-administration in rats (1999)
    Springer
    Psychopharmacology 142 (1999), S. 327-333 
    Details
    ISSN: 1432-2072
    Keywords: Key words Caffeine ; Nicotine self-administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The prevalence of tobacco smoking and coffee drinking place nicotine and caffeine among the most used licit drugs in many societies and their consumption is often characterised by concurrent use. The pharmacological basis for any putative interaction between these drugs remains unclear. Epidemiological reports support anecdotal evidence, which suggests that smokers consume caffeine to enhance the euphoric effects of nicotine. The aim of the present experiment was to examine effects of chronic exposure to caffeine on responding maintained by nicotine. Sprague-Dawley rats consuming caffeine (approximately 150–180 mg/kg per day) in their drinking water for 7 days prior to the beginning and throughout behavioural testing acquired intravenous nicotine self-administration (0.03 mg/kg per infusion) more rapidly than did controls. In a cross-over design, exclusion of caffeine brought levels of nicotine self-administration back to baseline, while adding caffeine to the drinking water of control rats increased responding maintained by nicotine over 90%. These findings strongly suggest that caffeine can potentiate the reinforcing properties of nicotine, thus highlighting the importance of environmental factors in shaping and maintaining tobacco smoking.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050896
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  • 8
    Electronic Resource
    Electronic Resource
    Adrenalectomy attenuates nicotine-induced dopamine release and locomotor activity in rats (1996)
    Springer
    Psychopharmacology 128 (1996), S. 343-350 
    Details
    ISSN: 1432-2072
    Keywords: Key words Addiction ; Microdialysis ; Behaviour ; Nucleus accumbens ; Corticosterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adrenalectomy (ADX) in mice can potentiate several physiological and behavioural responses to nicotine. The present experiments sought to examine this issue in the rat by characterising the influence of ADX upon the locomotor depressant, activating and dopamine-releasing properties of nicotine. Nicotine (0.8–1.2 mg/kg SC) dose-dependently depressed locomotor activity, an effect that was potentiated by ADX, while the locomotor activating effects of a smaller dose (0.4 mg/kg) were attenuated by ADX. In both SHAM and ADX rats chronically treated with nicotine for 5 days (daily injections of 0.4 mg/kg SC), the locomotor depressant effects of nicotine did not differ from saline-treated controls. Nicotine (0.4 mg/kg SC) increased extracellular levels of dopamine in the nucleus accumbens. This response was unaffected in rats pretreated with nicotine for 5 days (daily injections of 0.4 mg/kg SC). However, both ADX groups of rats showed smaller increases in dopamine following administration of nicotine. The results suggest that depletion of circulating corticosteroids can modulate sensitivity to nicotine in rats. The suppressant effects of ADX on nicotine-induced locomotor activity may be due to its effects on dopamine release in the nucleus accumbens.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050143
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  • 9
    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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  • 10
    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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