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  • 1
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Dihydro-β-erythroidine ; Locomotor activity ; Drug discrimination ; Operant behaviour
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of the nicotine antagonist dihydro-β-erythroidine (DHβE) was examined on various behavioural effects of nicotine in rats. Motor activity was recorded in photocell cages whereas discriminative stimulus effects were examined using two-lever drug discrimination procedures with a tandem schedule of food reinforcement (n = 8 throughout). DHβE (0.1–3.2 mg/kg) failed to antagonise the decreases in motor activity that nicotine (0.4–0.6 mg/kg) produced in experimentally naive rats, whereas mecamylamine (1.5 mg/kg) completely blocked this effect of nicotine. DHβE (0.1–3.2 mg/kg) antagonised the increases in motor activity that nicotine (0.4 mg/kg) produced in rats with extensive previous exposure to both nicotine and the photocell apparatus. In rats trained to discriminate either 0.1 or 0.4 mg/kg nicotine from saline, DHβE (0.1–3.2 mg/kg) blocked the discriminative stimulus effect of nicotine. The block of the discriminative effect could be reversed by increasing the dose of nicotine; DHβE (1.6 mg/kg) shifted the dose-response curve for nicotine discrimination to the right by a factor of 9.4. In addition, nicotine in doses of 0.32–0.64 mg/kg decreased the overall rate of lever pressing but DHβE (1.6 mg/kg) did not influence the dose-response curve for this effect. Thus, DHβE potently blocked the locomotor activating and discriminative stimulus effects of nicotine at doses that did not antagonise its locomotor depressant and operant response rate-reducing effects. This selective blockade supports the involvement of different subtypes of nicotinic receptor in the mediation of diverse behavioural effects. Furthermore, the rightward shift of the dose-response curve for nicotine discrimination suggested a competitive mode of action for DHβE.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Nicotine ; 1-Acetyl-4-methylpiperazine ; Mecamylamine ; DMPP ; Ligand binding ; Locomotor activity ; Drug discrimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The novel nicotinic agonist 1-acetyl-4-methylpiperazine (AMP) has been studied in ligand-binding and behavioural studies. AMP methiodide potently inhibited [3H]-(−)-nicotine and [125I]-α-bungarotoxin binding to P2 membranes from rat brain and [125I]-α-bungarotoxin binding to rat skeletal muscles. AMP HCl also inhibited nicotinic binding, but it was 100 times less potent than AMP methiodide. In behavioural studies, AMP HCl reduced locomotor activity of experimentally naive rats and mecamylamine blocked this effect. In rats receiving (−)-nicotine chronically, AMP HCl did not increase locomotor activity consistently or to the same extent as (−)-nicotine. In rats trained to discriminate (−)-nicotine from saline in a two-bar operant conditioning procedure with food reinforcement, there was generalization to AMP HCl, but only at doses that reduced the overall rate of responding. The potency and effectiveness of AMP relative to (−)-nicotine varied across the different behavioural procedures. The results suggest that the pharmacodynamic action of AMP differs from that of (−)-nicotine and that it usefully extends the range of agonists that can be used as probes for central nicotinic mechanisms.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Nicotine ; N-(3-pyridylmethyl)pyrrolidine ; Isoarecolone ; Nicotinic receptors ; Locomotor activity ; Drug discrimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The nicotinic agonists N-(3-pyridylmethyl)pyrrolidine (PMP) and isoarecolone have been compared with (−)-nicotine in three behavioural procedures and as inhibitors of [3H]-(−)-nicotine binding. Locomotor activity was recorded as movements between beams of infra-red light (ambulation). In experimentally naive rats, nicotine, PMP and isoarecolone reduced ambulation. In rats receiving nicotine chronically and previously exposed to the activity cages, nicotine and PMP increased ambulation in a dose-related manner. However, isoarecolone did not increase ambulation at doses that were active in other procedures. In rats trained to discriminate nicotine from saline in a two-bar operant conditioning procedure with food reinforcement, there was full generalization to PMP. It was also found that PMP potently inhibited the binding of [3H]-(−)-nicotine to rat brain membranes in vitro. These results were discussed with previous data for the discriminative stimulus and ligand-binding effects of isoarecolone obtained under similar conditions. The relative potency of PMP in different behavioural procedures was similar to that of (−)-nicotine. However, isoarecolone was relatively 10 times more potent in decreasing ambulation than would have been expected from its potency in the ligand-binding and discriminative stimulus procedures. The results suggest that the pharmacodynamic action of isoarecolone differs from that of nicotine and PMP, and that it will be a useful probe in further analyses of central nicotinic mechanisms.
    Type of Medium: Electronic Resource
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