Browsing by Author "Petro, Ann"

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    Chronic infusions of mecamylamine into the medial habenula: Effects on nicotine self-administration in rats.
    (Behavioural brain research, 2022-01) Levin, Edward D; Wells, Corinne; Slade, Susan; Johnson, Joshua; Petro, Ann; Rezvani, Amir H; Rose, Jed E
    The habenula is an epithalamic structure through which descending connections go from the telencephalon to the brainstem, putting it in a key location to provide feedback control over the ascending projections from the brainstem to the telencephalon. The medial habenula has a high concentration of nicotinic receptors. We assessed the role of medial habenular nicotinic receptors for nicotine self-administration (SA) in female young adult Sprague-Dawley rats. The rats had bilateral chronic infusion cannulae placed into the medial habenula nucleus. Each cannula was connected to a slow delivery osmotic minipump to chronically infuse mecamylamine (100 µg/side/day) or vehicle for four consecutive weeks. The rats were tested for nicotine SA for the first two weeks of mecamylamine infusion. Then, they had one week of enforced abstinence, during which they had no access to the nicotine SA. Finally, they had one week of resumed nicotine SA access. There was a significantly differential mecamylamine effects in animals with lower and higher pretreatment baseline nicotine SA. Rats with lower baseline nicotine SA levels showed a nearly significant mecamylamine-induced reduction in SA while those with higher baseline levels of SA showed a significant mecamylamine-induced increase in nicotine SA. This study determined that medial habenular nicotinic receptors are important for nicotine reinforcement. Baseline level of performance makes a crucial difference for the involvement of habenular mechanisms in nicotine reinforcement with nicotinic activation being important for maintaining nicotine self-administration for those with lower levels of baseline self-administration and the opposite effect with subjects with higher levels of baseline self-administration.
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    Impact of acute nicotine exposure on monoaminergic systems in adolescent and adult male and female rats.
    (Neurotoxicology and teratology, 2022-09) Eddins, Donnie; Petro, Ann; Levin, Edward D
    Adolescence is a period of risk for beginning tobacco addiction. Differential neural response to nicotine in adolescents vs. adults may help explain the increased vulnerability to nicotine self-administration seen with adolescent onset. We indexed the effects of acute nicotine ditartrate (0.4 mg/kg, salt weight) administration on dopamine (DA) and serotonin (5HT) as well as the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in several brain regions (nucleus accumbens, striatum and frontal cortex) of 6-week old (adolescent) and 10-week old (young adult) Sprague-Dawley rats. When nicotine was administered DA concentrations in the accumbens were significantly higher in adults than in adolescents, whereas there was no age-related difference without nicotine. However neither age group showed a significant effect of nicotine vs. age-matched controls. DA turnover in the accumbens was significantly greater in adolescent females in response to nicotine, but adult females did not show this effect and neither did males of either age group. DA turnover in the striatum was significantly higher in adolescents than adults regardless of nicotine administration. In the frontal cortex, there was a more complex effect. Without nicotine, adult male rats had higher DA concentrations than adolescent males, whereas female rats did not differ from adolescent to adult ages. When given nicotine, the age effect was no longer seen in males. However, there was not a significant effect of nicotine vs. age-matched controls in either age group. No age or nicotine effects were seen in females. 5HT in the accumbens was significantly increased by nicotine administration in adults but not in adolescents. Altered neural responsivity of adolescents to nicotine-induced neural effects particularly in accumbens DA and 5HT may be related to the increased nicotine dose concentrations they self-administer.
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    Persisting neurobehavioral effects of developmental copper exposure in wildtype and metallothionein 1 and 2 knockout mice.
    (BMC pharmacology & toxicology, 2016-11) Petro, Ann; Sexton, Hannah G; Miranda, Caroline; Rastogi, Anit; Freedman, Jonathan H; Levin, Edward D

    Background

    Metallothioneins (MT) are small proteins, which are crucial for the distribution of heavy and transition metals. Previously, we found in mice that knockout of MT 1 and 2 genes (MTKO) impaired spatial learning and potentiated the learning impairment caused by developmental mercury exposure. The current study examined the neurocognitive and neurochemical effects of MTKO with the developmental copper (Cu) supplementation.

    Methods

    Wildtype (WT) and MTKO mice were given supplemental Cu (0, 10 or 50 mg/l) in their drinking water during gestation and until weaning. When the mice were young adults they were trained on the win-shift 8-arm radial maze test of spatial learning and memory. After cognitive testing, their brains were analyzed for norepinepherine, dopamine and serotonin levels.

    Results

    In the spatial learning test, wildtype mice showed the normal sex difference with males performing more accurately than the females. This effect was eliminated by MTKO and restored by moderate Cu supplementation during development. In neurochemical studies, MTKO caused a significant overall increase in serotonin in all of the regions studied: the frontal cortex, posterior cortex, hippocampus, striatum, midbrain, and brainstem. MTKO also caused a significant increase in norepinepherine in the brainstem and hippocampus. In wildtype mice, Cu supplementation during development caused a significant decline in dopamine and norepinepherine in the midbrain and dopamine in the frontal cortex. These effects were blocked by MTKO.

    Conclusions

    The normal sex difference in spatial working memory accuracy, which was eliminated by MTKO, was restored by moderate copper supplementation. MTKO increased serotonin across all brain areas studied and increased norepinepherine only in the hippocampus and brainstem. MTKO blocked copper-induced decreases in dopamine and norepinepherine in the midbrain and dopamine in the frontal cortex.