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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Rats raised in an enriched environmental condition (EC) exhibit a decreased (35%) maximal velocity (Vmax) of [3H]dopamine (DA) uptake in medial prefrontal cortex (mPFC) compared with rats raised in an impoverished condition (IC); however, no differences between EC and IC groups in Vmax for [3H]DA uptake were found in nucleus accumbens and striatum. Using biotinylation and immunoblotting techniques, the present study examined whether the brain region-specific decrease in DA transporter (DAT) function is the result of a reduction in DAT cell surface expression. In mPFC, nucleus accumbens and striatum, total DAT immunoreactivity was not different between EC and IC groups. Whereas no differences in cell surface expression of DAT were found in nucleus accumbens and striatum, DAT immunoreactivity in the biotinylated cell surface fraction of mPFC was decreased (39%) in EC compared with IC rats, consistent with the magnitude of the previously observed decrease in Vmax for [3H]DA uptake in mPFC in EC rats. These results suggest that the decrease in DAT cell surface expression in the mPFC may be responsible for decreased DAT function in the mPFC of EC compared with IC rats, and that there is plasticity in the regulatory mechanisms mediating DAT trafficking and function.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Morphine ; Conditioned taste aversion ; Opioid-mediated analgesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The process of selective associations is evident in the aversive conditioning literature, where it has been shown that external cues are readily associated with peripheral pain, whereas taste cues are more easily associated with effects of drug administration. Within this framework, it is of interest that the failures to obtain a conditioned analgesic response to a morphine-associated CS have used external cues as conditioned stimuli. In Experiment 1, subjects re-exposed to a morphine-associated CS not only expressed the anticipated taste aversion, but also exhibited a decrease in pain sensitivity that was evident 15 or 30 min following CS re-exposure. Experiment 2 suggested that the conditioned analgesic response was opioid mediated, as pre-test administration of naloxone blocked expression of the analgesic CR. In Experiment 3, an increase in opiate receptor sensitivity produced by chronic naltrexone treatment did not affect the strength of the taste aversion, but resulted in an increase in the magnitude of the conditioned analgesic response. Collectively, these data suggest a neuropharmacological dissociation in systems mediating the two responses.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Nornicotine ; Behavioral sensitization ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Nicotine, a tobacco alkaloid, is known to be important in the acquisition and maintenance of tobacco smoking. Nornicotine, an active nicotine metabolite, stimulates nicotinic receptors and may produce psychomotor effects similar to nicotine. Objective: The present study determined the effects of acute and repeated administration of nornicotine on locomotor activity and compared its effects with those of nicotine. Methods: R(+)-Nornicotine (0.3–10 mg/kg), S(–)-nornicotine (0.3–10 mg/kg), S(–)-nicotine (0.1–1 mg/kg) or saline was administered s.c. to rats acutely or repeatedly (eight injections at 48-h intervals). Activity was recorded for 50 min immediately after each injection. Results: S(–)-Nicotine produced transient hypoactivity, followed by dose-related hyperactivity. Repeated S(–)-nicotine administration resulted in tolerance to the hypoactivity and sensitization to the hyperactivity. Subsequent testing following a saline injection revealed evidence of conditioned hyperactivity. Acute administration of 0.3 mg/kg or 1 mg/kg R(+)- or S(–)-nornicotine produced no effect. Transient hypoactivity was observed at 3 mg/kg and 10 mg/kg R(+)-nornicotine and at 10 mg/kg S(–)-nornicotine. However, rebound hyperactivity was not observed following acute administration of either nornicotine enantiomer, suggesting that nornicotine-induced psychomotor effects differ qualitatively from those of S(–)-nicotine. Repeated R(+)-nornicotine resulted in tolerance to the transient hypoactivity, however hyperactivity was not observed. Repeated S(–)-nornicotine resulted in tolerance to the hypoactivity and the appearance of hyperactivity. Repeated administration of either nornicotine enantiomer resulted in a dose-dependent alteration in response to a 1 mg/kg S(–)-nicotine challenge, suggesting some commonalities in the mechanism of action. Conclusion: Nornicotine likely contributes to the neuropharmacological effects of nicotine and tobacco use.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: EEDQ ; Dopamine ; Amphetamine ; Ontogeny ; Rat pups
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous research has shown that the alkylating agentN-ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline (EEDQ) affects dopamine (DA) synthesis and metabolism in both preweanling and adult rats. In the present study, we attempted to determine the behavioral relevance of EEDQ's presynaptic actions. To that end, 17- and 90-day-old rats were injected with either EEDQ (7.5 mg/kg, IP) or its vehicle 30 min after half the rats were pretreated with the selective DA antagonists SCH 23390 and sulpiride. (SCH 23390/sulpiride pretreatment was used to protect D1 and D2 receptors from EEDQ-induced inactivation.) The behavioral effects of amphetamine (0, 0.1, 0.3, or 1.0 mg/kg, IP) were then assessed 1, 2, 4, and 8 days after EEDQ treatment. Amphetamine-induced behaviors were used to assess EEDQ's presynaptic actions, because amphetamine does not directly bind to the DA receptor, but rather releases DA from the presynaptic terminal. Further, since half of the EEDQ-treated rats had a full complement of DA receptors (i.e., those rats pretreated with SCH 23390/sulpiride), EEDQ's actions in the presynaptic terminal could be dissociated from actions at pre- and postsynaptic receptors. In general, the results showed that EEDQ blocked most of the amphetamine-induced behaviors of both 17- and 90-day-old rats. Surprisingly, pretreatment with SCH 23390 and sulpiride only protected the amphetamine-induced behaviors of adult rats, but not the behaviors of 17-day-old rat pups. When considered together, these results suggest that EEDQ's presynaptic effects are not behaviorally relevant to the adult rat, but may be responsible for eliminating amphetamine-induced behaviors in the 17-day-old rat pup.
    Type of Medium: Electronic Resource
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