Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Nov 2011
Comparative StudyExtended access methamphetamine decreases immature neurons in the hippocampus which results from loss and altered development of neural progenitors without altered dynamics of the S-phase of the cell cycle.
Methamphetamine addicts demonstrate impaired hippocampal-dependent cognitive function that could result from methamphetamine-induced maladaptive plasticity in the hippocampus. Reduced adult hippocampal neurogenesis observed in a rodent model of compulsive methamphetamine self-administration partially contributes to the maladaptive plasticity in the hippocampus. The potential mechanisms underlying methamphetamine-induced inhibition of hippocampal neurogenesis were identified in the present study. ⋯ Methamphetamine concomitantly increased hippocampal apoptosis, changes that were evident during the earlier days of self-administration. These findings demonstrate that methamphetamine self-administration initiates allostatic changes in adult neuroplasticity maintained by the hippocampus, including increased apoptosis, and altered dynamics of hippocampal neural progenitors. These data suggest that altered hippocampal plasticity by methamphetamine could partially contribute to methamphetamine-induced impairments in hippocampal function.
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Pharmacol. Biochem. Behav. · Nov 2011
Comparative StudyUse of the light-dark box to compare the anxiety-related behavior of virgin and postpartum female rats.
Postpartum female rodents are less anxious than diestrous virgins and this difference contributes to dams' ability to adequately care for pups and defend the nest. Low postpartum anxiety has been observed in many behavioral paradigms but the results of previous studies using the light-dark box have been inconsistent. We here reexamined the usefulness of the light-dark box to assess differences between postpartum and diestrous virgin female rats in their anxiety-related behavior. ⋯ We then examined if dams' low-anxiety behavior in the light-dark box depends on high GABA(A) receptor activity by inhibiting the receptor at different binding sites using (+)-Bicuculline to target the GABA site, FG-7142 to target the benzodiazepine site, and pentylenetetrazol to target the picrotoxin site. Only pentylenetetrazol was consistently anxiogenic in dams, while having little effect in diestrous virgins. Thus, the light-dark box can be a useful paradigm to study differences between postpartum and diestrous virgin female rats in their anxiety-related behaviors, and this difference is influenced by dams' recent contact with pups and GABA(A) receptor neurotransmission particularly affected by activity at the picrotoxin site.
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Pharmacol. Biochem. Behav. · Nov 2011
Comparative StudyThe smoking cessation drug varenicline improves deficient P20-N40 inhibition in DBA/2 mice.
Varenicline, an FDA approved smoking cessation pharmacotherapy, is an α4β2* nicotinic acetylcholine receptor (nAChR) partial agonist and an α7* nAChR full agonist. Both subtypes of nAChR are involved in modulating auditory evoked responses in rodents. In DBA/2 mice, an inbred strain, auditory evoked responses to paired auditory stimuli fail to inhibit to the second stimulus. ⋯ Selective blockade of either the α4β2* or α7* nAChR in competition with 0.6mg/kg varenicline prevented varenicline induced improvements. In competition with a higher dose of varenicline (3mg/kg) only blockade of the α4β2* nAChR prevented varenicline induced improvement in auditory evoked response inhibition. These data indicate the importance of α4β2* nAChRs and the potential involvement of the α7* subtype in varenicline's effects on auditory evoked responses in DBA/2 mice.
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Pharmacol. Biochem. Behav. · Nov 2011
Comparative StudyMaternal prolactin inhibition at the end of lactation affects learning/memory and anxiety-like behaviors but not novelty-seeking in adult rat progeny.
Maternal hypoprolactinemia at the end of lactation in rats reduces milk production and is associated with offspring's malnutrition. Since malnutrition during development is also known to have long lasting effects on cognition and emotion, in the present study we tested the hypothesis that maternal hypoprolactinemia, induced by bromocriptine treatment, at the end of the lactating period affects memory/learning, novelty-seeking and anxiety-like behaviors in adult male Wistar rats using, respectively, the radial arm water maze (RAWM), the hole board (HB) arena and the elevated plus-maze (EPM). We also analyzed serum corticosterone and thyroid hormone levels at postnatal day (PN) 21. ⋯ No difference was observed between groups regarding the number of nose-pokes in the HB. In the EPM, BRO rats stayed less time in and had fewer entries into the open-arms than CON ones. This pattern of results indicates that maternal bromocriptine treatment at the end of the lactating period results in poorer memory/learning performance and in higher levels of anxiety-like behavior in the adult offspring, demonstrating that even a relatively short period of malnutrition during development can have long lasting detrimental effects regarding cognition and emotion.
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Pharmacol. Biochem. Behav. · Nov 2011
Comparative StudyAntinociceptive effects of intragastric DL-tetrahydropalmatine on visceral and somatic persistent nociception and pain hypersensitivity in rats.
Although tetrahydropalmatine (THP), an alkaloid constituent of plants from the genera Stephania and Corydalis, is known to have analgesic property, the antinociceptive effects of THP have not been well evaluated experimentally and the appropriate indications for treatment of clinical pain remain unclear. In the present study, nociceptive and inflammatory models of both somatic and visceral origins were used to assess the antinociceptive and antihyperalgesic effects of intragastric (i.g.) pretreatment of dl-THP in rats. In the bee venom (BV) test that has been well established experimentally, i.g. pretreatment of three doses of dl-THP (20, 40, 60 mg/kg, body weight) resulted in less stably antinociceptive effect on the BV-induced persistent paw flinches that are known to be processed by spinal nociceptive circuit, however the drug of the two higher doses produced distinct suppression of the BV-induced persistent nociception rated by nociceptive score that reflects both spinal and supraspinal mediation. ⋯ In the acetic acid writhing test, the number of writhes was completely blocked at the first 5-min interval followed by a sustained suppression in the remaining period of the whole time course comparing to the vehicle control. These data suggest that i.g. pre-administration of dl-THP could more effectively inhibit visceral nociception as well as thermal and mechanical inflammatory pain hypersensitivity (hyperalgesia) than persistent nociception. Moreover, the drug is likely to produce more effectiveness on supraspinally processed nociceptive behaviors than spinally mediated nociceptive behaviors, implicating an action of THP at the supraspinal level.