Evidence for elevated nicotine-induced structural plasticity in nucleus accumbens of adolescent rats
ABSTRACT Male Long-Evans rats were administered nicotine bitartrate or sodium tartrate either during adolescence (p29-43) or adulthood (p80-94). Route of administration was via subcutaneously implanted osmotic pump (initial dose 2.0 mg/kg/day, free base). Five weeks following nicotine administration, brains were processed for Golgi-Cox staining. Medium spiny neurons from nucleus accumbens (NAc) shell were digitally reconstructed for morphometric analysis. Total dendritic length and branch number were greater in medium spiny neurons from animals pretreated with nicotine during adolescence. A branch order analysis indicated that increased branch number was specific to higher order branches. Mean branch lengths did not differ with respect to treatment as a function of branch order. Thus, nicotine-induced increases in total dendritic length were a function of greater numbers of branches, not increased segment length. In contrast, adult nicotine exposure did not significantly alter total dendritic length or branch number of medium spiny neurons. Total dendritic length and branch number of a second morphological type, the large aspiny neuron, did not differ following either adolescent or adult pretreatment. The age-dependent alteration of accumbal structure was associated with qualitatively different behavioral responses to drug challenge. These data provide evidence that drug-induced structural plasticity in nucleus accumbens is considerably more pronounced during adolescence.
- SourceAvailable from: Hadley Creighton Bergstrom
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- "Although the magnitude of increased total dendritic length (25 %) observed at this late time-point appears lower than that observed at the early time-point (54 %), it should be noted that this largely reflects continued growth of MSN dendritic length in control animals (*13 %) rather than a reduction in dendritic length of MSNs from nicotine-treated animals, consistent with the presence of continued neural development during adolescence (Ojeda and Urbanski 1994; Bergstrom et al. 2010; Koss et al. 2014). Previous research has demonstrated that adult nicotine exposure also induces dendrite remodeling in the nucleus accumbens shell when measured at remote time-points (Brown and Kolb 2001; McDonald et al. 2007), and although these alterations are of lower overall magnitude we would expect the overall trajectory of dendrite remodeling to follow a similar pattern as in the present study. However, the continued developmental pattern in NAcc MSNs might be an important factor mediating the enhanced vulnerability of the adolescent brain to nicotine-induced dendritic remodeling and other neurobehavioral effects of nicotine exposure (O'Dell 2009). "
ABSTRACT: Chronic nicotine exposure during adolescence induces dendritic remodeling of medium spiny neurons (MSNs) in the nucleus accumbens (NAcc) shell. While nicotine-induced dendritic remodeling has frequently been described as persistent, the trajectory of dendrite remodeling is unknown. Specifically, no study to date has characterized the structural plasticity of dendrites in the NAcc immediately following chronic nicotine, leaving open the possibility that dendrite remodeling emerges gradually over time. Further, the neuropharmacological mechanisms through which nicotine induces dendrite remodeling are not well understood. To address these questions, rats were co-administered chronic nicotine (0.5 mg/kg) and the D1-dopamine receptor (D1DR) antagonist SCH-23390 (0.05 mg/kg) subcutaneously every other day during adolescence. Brains were then processed for Golgi-Cox staining either 1 day or 21 days following drug exposure and dendrites from MSNs in the NAcc shell digitally reconstructed in 3D. Spine density was also measured at both time points. Our morphometric results show (1) the formation of new dendritic branches and spines 1 day following nicotine exposure, (2) new dendritic branches, but not spine density, remains relatively stable for at least 21 days, (3) the co-administration of SCH-23390 completely blocked nicotine-induced dendritic remodeling of MSNs at both early and late time points, suggesting the formation of new dendritic branches in response to nicotine is D1DR-dependent, and (4) SCH-23390 failed to block nicotine-induced increases in spine density. Overall this study provides new insight into how nicotine influences the normal trajectory of adolescent brain development and demonstrates a persistent form of nicotine-induced neuroplasticity in the NAcc shell that develops rapidly and is D1DR dependent.Brain Structure and Function 09/2014; DOI:10.1007/s00429-014-0897-3 · 4.57 Impact Factor
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- "In rats that were sacrificed for anatomical analysis on P144 following continuous exposure to nicotine from the juvenile period to young adulthood (P22–69) via an osmotic minipump (2 mg/kg/ day), medium spiny neurons of the NAc had more and longer dendritic segments compared to saline-exposed controls (McDonald et al., 2005). Subsequently, this same group demonstrated that nicotine-induced increases in dendritic length and branch number in medium spiny neurons was selectively increased in rats exposed from P29 to P43, but not in those exposed from P80 to P94 (McDonald et al., 2007). In the mPFC, and more specifically pyramidal cells of the prelimbic cortex, continuous exposure to nicotine during adolescence (P29–43) increases the length of basilar dendrites in cells classified as ''complex'' because of their large dendritic arbor. "
ABSTRACT: Adolescence is a period of significant neurobiological change that occurs as individuals transition from childhood to adulthood. Because the nervous system is in a relatively labile state during this stage of development, it may be especially sensitive to experience-induced plasticity. One such experience that is relatively common to adolescents is the exposure to drugs of abuse, particularly alcohol and psychostimulants. In this review, we highlight recent findings on the long-lasting effects of exposure to these drugs during adolescence in humans as well as in animal models. Whenever possible, our focus is on studies that use comparison groups of adolescent- and adult-exposed subjects as this is a more direct test of the hypothesis that adolescence represents a period of enhanced vulnerability to the effects of drug-induced plasticity. Lastly, we suggest areas of future investigation that are needed and methodological concerns that should be addressed.Neuroscience 05/2013; 249. DOI:10.1016/j.neuroscience.2013.05.026 · 3.33 Impact Factor
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- "Nucleus accumbens Nicotine ↑ dendritic length and branches Brown and Kolb, 2001; McDonald et al., 2007 Prefrontal cortex "
ABSTRACT: Addictive drugs can activate systems involved in normal reward-related learning, creating long-lasting memories of the drug's reinforcing effects and the environmental cues surrounding the experience. These memories significantly contribute to the maintenance of compulsive drug use as well as cue-induced relapse which can occur even after long periods of abstinence. Synaptic plasticity is thought to be a prominent molecular mechanism underlying drug-induced learning and memories. Ethanol and nicotine are both widely abused drugs that share a common molecular target in the brain, the neuronal nicotinic acetylcholine receptors (nAChRs). The nAChRs are ligand-gated ion channels that are vastly distributed throughout the brain and play a key role in synaptic neurotransmission. In this review, we will delineate the role of nAChRs in the development of ethanol and nicotine addiction. We will characterize both ethanol and nicotine's effects on nAChR-mediated synaptic transmission and plasticity in several key brain areas that are important for addiction. Finally, we will discuss some of the behavioral outcomes of drug-induced synaptic plasticity in animal models. An understanding of the molecular and cellular changes that occur following administration of ethanol and nicotine will lead to better therapeutic strategies.Frontiers in Molecular Neuroscience 11/2012; 5:83. DOI:10.3389/fnmol.2012.00083 · 4.08 Impact Factor