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  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    157—Drugs of Abuse: Toxicity and Structural Plasticity

    Sunday, November 10, 2013, 8:00 am - 12:00 noon

    157.10: Nicotine administration attenuates the object recognition deficits caused by methamphetamine in rats

    Location: Halls B-H

    1Dept. of Pharmacol. and Toxicology, 2Sch. of Dent., Univ. of Utah, Salt Lake City, UT

    Abstract Body: Repeated methamphetamine (METH) administrations cause persistent hippocampal serotonergic and cognitive deficits. Noteworthy, although the majority of METH abusers smoke cigarettes, few preclinical studies have investigated the neurochemical and behavioral interaction between the use of nicotine (NIC) and METH. Extensive clinical and preclinical assessments of cognition have revealed the important role of the cholinergic system and the hippocampus in working memory. Furthermore, NIC has been studied for its ability to improve memory. Accordingly, the present study investigated the effects of NIC administration on METH-induced persistent cognitive and serotonergic deficits. Male Sprague-Dawley rats received NIC administration in their drinking water from adolescence (post-natal day (PND) 40) through adulthood (PND 97), or regular tap water. At PND 90, rats received either a high-dose METH regimen or saline. On PND 96, animals underwent novel object recognition testing. On PND 97, animals were sacrificed and hippocampal serotonin transporter (SERT) function and 5-HT content were assessed. Results revealed that chronic NIC pre-treatment + post-treatment attenuates METH-induced cognitive deficits but not hippocampal serotonergic deficits. Further investigation is necessary to elucidate the mechanisms by which NIC pre-treatment attenuates cognitive deficits caused by METH.

    Lay Language Summary: Our results revealed that chronic nicotine administration to rats attenuates short-term memory deficits but not serotonin deficits caused by methamphetamine exposure.
    Methamphetamine abuse is a significant issue for the health care and criminal justice systems that has led to high economic costs. Clinical and preclinical studies have demonstrated that methamphetamine abuse can cause persistent serotonergic, as well as cognitive deficits. Noteworthy, many methamphetamine abusers also smoke cigarettes and thus self-administer nicotine. However, few in vivo preclinical studies have evaluated the behavioral and neurochemical interaction between these drugs.
    Nicotine is an addictive substance in cigarettes that non-selectively binds to all subtypes of nicotinic receptors. Importantly, cigarette smoking often starts during adolescence, a period in which the brain is still under development. Neurochemical changes induced by cigarettes, particularly nicotine, potentially influence several aspects of the adult brain functioning and thus are worthy of investigation.
    It is important to point out that cigarettes contain several other substances besides nicotine and cigarette smoking increases the risk for cancers, respiratory and cardiovascular diseases. However, nicotine by itself in the form of patch, gum and lozenges are FDA-approved therapies for smoking cessation. Several clinical and preclinical studies have shown that nicotine and related agonists ameliorate cognitive deficits in Alzheimer’s disease and attention deficit hyperactivity disorder and afford stabilizing effects on schizophrenics.
    Of relevance are our findings that nicotine exposure throughout adolescence attenuate the persistent dopaminergic deficits caused by methamphetamine treatment. The present study extended these findings by investigating the effects of chronic nicotine administration on methamphetamine-induced persistent cognitive and serotonergic deficits. Male Sprague-Dawley rats received nicotine in their drinking water from adolescence (post-natal day (PND) 40) through adulthood (PND 97), or regular tap water. The dosing regimen was selected as it has been demonstrated to afford nicotine concentrations in the brain that are similar to moderate-heavy human smokers. At PND 90, rats received either a high-dose methamphetamine regimen (administered so as to mimic some aspects of human binging) or saline. On PND 96, animals underwent novel object recognition testing. On PND 97, hippocampal serotonin transporter function and serotonin content were assessed.
    Object recognition has been widely studied in rats and relies on the instinct of rats to spend more time exploring novel objects versus familiar objects. For this task to be performed successfully, rats have to remember which object is familiar.
    In summary, our studies revealed that chronic nicotine pretreatment to rats reduced the short-term memory deficits caused by a high-dose methamphetamine administration. In contrast, nicotine did not attenuate the methamphetamine-induced hippocampal serotonergic deficits suggesting that these neurons do not mediate the effect of nicotine on short-term memory.