SYNAPSE 69:607–610 (2015)
Short Communication
Changes in Dendritic Spine Density in the Nucleus Accumbens Do Not Underlie Ethanol Sensitization N. NOBREGA1,2,3,4* CHRISTINA N. NONA,1,2 MARIE KRISTEL BERMEJO,1 AMY J. RAMSEY,1 AND JOSE 1 Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada 2 Behavioural Neurobiology Laboratory, Campbell Family Mental Health Research Institute, CAMH, Toronto, Ontario, Canada 3 Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada 4 Department of Psychology, University of Toronto, Toronto, Ontario, Canada
KEY WORDS
spine density; ethanol; locomotor sensitization; nucleus accumbens
ABSTRACT Behavioral sensitization to various drugs of abuse has been shown to change dendritic spine density and/or morphology of nucleus accumbens (NAc) medium spiny neurons, an effect seen across drug classes. However, is it not known whether behavioral sensitization to ethanol (EtOH) is also associated with structural changes in this region. Here we compared dendritic spine density and morphology between mice showing High vs. Low levels of EtOH sensitization and found that high levels of EtOH sensitization were not associated with changes in dendritic spine density or spine type. Unexpectedly, however, a significant increase in the density of stubby-type spines was seen in mice that were resistant to sensitization. Since the presence of this spine type has been associated with long-term depression and cognitive/learning deficits this may explain why these mice fail to sensitize and why they show poor performance in conditioning tasks, as previously shown. A possible causal role for structural plasticity in behavioral sensitization to various drugs has been debated. In the case of EtOH sensitization, our results suggest that drug-induced changes in structural plasticity in the accumbens neurons may not be the cause of sensitized behavior. Synapse 69:607–610, 2015. VC 2015 Wiley Periodicals, Inc. INTRODUCTION Excitatory neurotransmission within the CNS occurs primarily at dendritic spines, small protrusions from the dendrite which receive and modulate synaptic input (Bito, 2010). The morphology and number of spines have been shown to be critical to the function of individual synapses, modulating neuron activity at the molecular, neuronal, circuit, systems, and behavioral levels (Spiga et al., 2014a). Enduring behavioral changes, believed to arise from reorganization of synaptic connections (Hofer and Bonhoeffer, 2010; Kasai et al., 2010) have often been accompanied by persistent and stable changes in dendritic structure. An example of an enduring behavioral change is behavioral sensitization, which occurs when repeated drug administration produces a progressive and longlasting increase in the locomotor response to the drug (Robinson and Kolb, 2004). Behavioral sensitization to various drugs of abuse has been shown to change dendritic spine density and/or morphology of nucleus Ó 2015 WILEY PERIODICALS, INC.
accumbens (NAc) medium spiny neurons (MSNs), an effect seen across drug classes (Robinson and Kolb, 2004). However, is it not known whether behavioral sensitization to ethanol (EtOH) is also associated with structural changes in this region. One distinctive property of EtOH sensitization is the presence of significant inter-individual variability in the sensitization response, with some mice being susceptible (high-sensitization, HS) and others resistant (low-sensitization, LS) (Hitzemann and Hitzemann, 1997; Masur and Lodder Martins dos Santos, 1988; Nona et al., 2013). Here we compared dendritic spine Contract grant sponsor: NSERC; Contract grant number: RGPIN-2015– 06615. *Correspondence to: Jose N. Nobrega, Behavioural Neurobiology Laboratory, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ont M5T 1R8, Canada. E-mail:
[email protected] Received 3 July 2015; Revised 31 July 2015; Accepted 25 August 2015 DOI: 10.1002/syn.21862 Published online 14 October 2015 in Wiley Online Library (wileyonlinelibrary. com).
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Fig. 1. Behavioral sensitization to EtOH. A: Development of EtOH sensitization: EtOH-treated mice were classified as HS or LS based on their scores for injection 7. Repeated measures ANOVA indicated a significant main effects of injection day [F (4, 60)510.48, P < 0.001], treatment [F(2, 15) 5 15.33, P 5 0.00], injection day by treatment interaction [F(2, 15) 5 38.88, P < 0.001]. *P < 0.05; **P
