Psychopharmacology
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Local anesthetics bind to the dopamine transporter (DAT), inhibit dopamine (DA) uptake and have been reported to have cocaine-like discriminative stimulus effects. The hypothesis of the present study was that affinity at the DAT and potency as a DA uptake blocker determines potency as a cocaine-like discriminative stimulus among local anesthetics, and maximum DA uptake inhibition determines maximum cocaine-like discriminative stimulus effects. ⋯ Cocaine-like discriminative stimulus effects of local anesthetics were more prominent at a low than at a high training dose of cocaine. Sodium channels seem to have a direct influence on discriminative effects at low cocaine doses, whereas they have an indirect influence on discriminative effects at high cocaine doses by decreasing response rates.
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The pharmacological profile of risperidone is that of an atypical neuroleptic regarding its serotonin 5-HT2A and dopamine D2 receptor blocking properties. Treatment with risperidone, though, results in considerably elevated plasma prolactin (PRL) levels which are not observed with other atypical neuroleptics, such as clozapine, indicating a differentiated action on receptors that are involved in PRL release, mainly dopaminergic and serotonergic. ⋯ During treatment with typical neuroleptics, the PRL responses to clomipramine are normal, and they are preserved after switch to risperidone in doses that cause complete dopamine receptor blockade. Risperidone, a dopamine and 5-HT receptor blocker, does not affect 5-HT receptors that are involved in the PRL release by the 5-HT uptake blocker clomipramine, indicating a different behavior than other atypical neuroleptics such as clozapine or olanzapine, for which a reduction of the PRL release induced by serotonergic agents like fenfluramine or mCPP has been reported. A conclusive identification of the 5-HT receptor subtypes that are involved in this different action cannot be identified at present, but it should be taken into account that risperidone differs from clozapine, showing higher affinity for 5-HT2A than 5-HT2C receptors and lacking the marked affinity of clozapine to 5-HT1A receptors.
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Despite the widespread popularity of opioid analgesics, significant differences in the potency and effectiveness of these drugs are often observed across age groups. ⋯ These data may be taken as evidence that aged male rats are more sensitive to the antinociceptive effects of mu opioids than young male rats, and that age-related differences in opioid sensitivity are most apparent when lower efficacy opioids and higher nociceptive intensities are employed during behavioral testing.
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Acute administration of nicotine induces analgesia with subsequent development of tolerance. In human studies, females are less sensitive to the analgesic effects of nicotine than males. Few previous animal studies have investigated analgesic effects of chronic nicotine administration or addressed gender differences. ⋯ Chronic nicotine-induced analgesia was confirmed in both male and female rats as assessed using the hot-plate test which reflects integrated pain behavior. Males, but not females, exhibited analgesia in a nociceptive withdrawal reflex test (tail flick), indicating that nicotine-induced analgesia may depend on both the type of pain test and gender. The lack of nicotine-induced analgesia assessed by the tail flick reflex test in female rats is consistent with recent human studies showing that nicotine reduces pain elicited by brief noxious cutaneous stimulation in male but not female subjects.