Curtin, John J

Hachiya, Laura Y

Moberg, Christine A

Digital Commons@Becker

Washington University School of MedicineDigital Commons@BeckerPosters2010: Disentangling the Genetics of Alcoholism:Understanding Pathophysiology and ImprovingTreatment2010Alcohol effects on affective response duringvariable and fixed duration threatChristine A. MobergUniversity of Wisconsin - MadisonLaura Y. HachiyaUniversity of Wisconsin - MadisonJohn J. CurtinUniversity of Wisconsin - MadisonFollow this and additional works at: http://digitalcommons.wustl.edu/guzeposter2010Part of the Medicine and Health Sciences CommonsThis Poster is brought to you for free and open access by the 2010: Disentangling the Genetics of Alcoholism: Understanding Pathophysiology andImproving Treatment at Digital Commons@Becker. It has been accepted for inclusion in Posters by an authorized administrator of DigitalCommons@Becker. For more information, please contact engeszer@wustl.edu.Recommended CitationMoberg, Christine A.; Hachiya, Laura Y.; and Curtin, John J., "Alcohol effects on affective response during variable and fixed durationthreat" (2010). Posters. Paper 15 Samuel B. Guze Symposium on Alcoholism.http://digitalcommons.wustl.edu/guzeposter2010/15Alcohol Effects on Affective Response During Variable and Fixed Duration ThreatChristine A Moberg, Laura Y Hachiya, & John J CurtinABSTRACTRecent research indicates that fear and anxiety are distinct processes with separable neurobiological substrates. Experimental procedures using predictable vs. unpredictable shock administration have been used to elicit fear vs. anxiety, respectively (Grillon et al, 2004). Using these procedures, our lab has demonstrated that alcohol reduces anxiety to unpredictable shock but not fear to predictable shock (Moberg & Curtin, 2009). However, this manipulation of predictability varied both the probability and temporal precision of shock threat, raising critical questions as to which stimulus characteristics are central to both the elicitation of anxiety and the anxiolytic effects of alcohol.To disentangle these two characteristics, we developed a novel paradigm to systematically vary temporal occurrence of threat while holding the probability of threat occurrence constant.  Intoxicated (0.08% BAC), non-intoxicated, and placebo participants viewed a series of visual cues.  Fixed 5s cue presentations were equivalent to predictable shock cues that elicited fear in earlier research. Variable duration cues (5s, 20s, 50s, or 80s) were designed to elicit anxiety due to the temporal uncertainly of the threat occurrence. Startle potentiation (SP) relative to matched cue periods in no-shock blocks provided the primary measure of affective response.All shock cues produced robust SP.  Additionally, two key findings were observed. We first examined affective response during the first 4 seconds of the cue presentation, such that startle probe occurrence was matched between variable and fixed duration blocks.  We found that alcohol significantly reduced SP during variable duration threat cues, whereas there was no detectable alcohol effect during fixed duration threat cues.   We then examined affective response later during each variable duration cue.  We found that alcohol reduced SP during later time points in the longer cues, suggesting that the alcohol effects persist over time.These results build on evidence suggesting that fear and anxiety are distinct, separable affective responses, and suggest that anxiety can be elicited by altering either threat probability or temporal precision. Underscoring previous findings that alcohol selectively reduces anxiety but not fear, this work has important implications for high rates of comorbidity between anxiety disorders and alcoholism.BACKGROUND & HYPOTHESISStartle Reflex• The startle reflex is used to assess affective response to threat (e.g. electric shock; Davis, 1989; Grillon & Baas, 2004)• Startle potentiation (SP) is defined as the increase in startle response to an acoustic “Startle probe” during threat vs. no-threat conditions• SP is non-invasive, operates outside of consciousness, and can be assess across speciesFear vs. Anxiety• Phasic (brief) SP is observed when threat is highly predictable, certain, and imminent.  These manipulations have been used to model fear in the lab.• Sustained SP is observed when threats are more distal, tonic, uncertain, or otherwise unpredictable.  These manipulations have been used to model anxiety in the lab.• Animal models have implicated the central nucleus of the amygdala (CeA) in fearwhereas the bed nucleus of the stria terminalis (BNST) has been implicated in anxietyAlcohol Effects on Affective Response• Moberg and Curtin (2009) demonstrated that alcohol selectively reduced SP to uncertain but not certain threat cues using a manipulation of predictability• This unpredictability manipulation confounded threat probability with threat imminence.•A recent experiment by our lab (Hefner & Curtin, in prep) has demonstrated that alcohol reduces SP during blocks where threat occurs during 20% of cues but not during blocks on which participants are shocked on every trial• The current study aimed to further examine the aspect of threat imminence and whether alcohol equally affects proximal and distal threatsHypothesis•A moderate dose of alcohol will selectively reduce SP during stimuli of variable (unpredictable) durationMETHODParticipants• 72 social drinking undergraduates• Three beverage groups: Alcohol (target BAC: 0.08%), placebo, and no alcoholGeneral Procedure• All participants completed a pre-drink baseline startle assessment and a post-drink shock tolerance assessment• Participants viewed blocks of colored square “cue” presentations separated by an inter-trial interval•There were four types of block:1.  Variable duration shock (6 cues per block)2.  Variable duration no shock (6 cues per block)3.   Fixed duration shock (5 cues per block)4.   Fixed duration no shock (5 cues per block)Measures• EMG eyeblink startle response to noise probes was measured during both cue presentation and ITIs in all blocks.  Scored as peak response in 20-120ms post-probe onset.  •Potentiation scores are calculated as the startle response to a given probe during a shock block minus startle response magnitude to the corresponding probe during no shock blockStartle probes occurred at 4.5s during fixed duration blocksStartle probes occurred at 4.5s, 19.5s, 49.5s, and 79.5s during variable durationDuring shock cue presentations shocks occurred 0.25s before cue offset.Participants did not know the length of each specific cue during the variable cue blocks, only that cues could be 5, 20, 50, or 80 seconds.No Alcohol & PlaceboAlcohol First Sound ProbeAverage of Later Probes• The main effect of Block type was significant (p < .001).  Startle response during cues was significantly potentiated in both fixed shock  (p < .001) and variable shock (p < .001) blocks relative to fixed and variable no shock blocks• The Beverage group X Cue typeinteraction was significant (p = .019)• Within variable cue blocks, the Beverage effect is significant (p = .025)5s                50s                           20s                       80s= startle        = shock50s                      5s                   80s                                       20s5s              5s              5s            5s5s              5s 5s 5s• The Beverage group X Cue time interaction was not significant (p = .081)• The simple effect of beverage group on startle potentiation for the average of 4 later probes is not significant (p = .195)INTERPRETATIONS• Whereas alcohol does not reduce startle potentiationduring fixed duration threat cues, it does reduce potentiation to cues whose timing is unknown and potentially more distal• This study design also allowed us to demonstrate that participants’ startle potentiation is maintained over a long duration cue, extending a current animal model to humans• Animal models have identified the neural structures responsible for startle response to variable (long) duration cues.  The synthesis of the current results with the findings of such preclinical studies may help identify the brain structures which are affected by acute intoxication• Alcohol’s effects on the neurobiological substrates of anxiety may be one target for neuroplastic change supporting alcohol (and other drug) dependence.• This selective effect may account for the pattern of co-morbidity of alcohol use disorders with anxiety disorders.Analytic DesignBlock Type (within subjects): 4 typesCue Type (within subjects): 2 types (Fixed vs. Variable)Beverage Group (between subjects): 3 groups (No Alcohol, Placebo, and Alcohol), collapsed into 2 groups (No Alcohol & Placebo vs. Alcohol)0102030405060Fixed Cue Variable Cue (First Probe)Startle PotentiationRelative to No Shock (µV)Startle Potentiation By Beverage Group and Cue Type0102030405060Placebo & No Alcohol AlcoholStartle PotentiationRelative to No Shock (µV)Startle Potentiation During Variable Shock BlocksREFERENCESDavis, M. (1989). Annals of NY Academy of Sciences, 563,165-183.Grillon, C., et al. (2004). Behavioral Neuroscience, 118 (5), 916-924.Hefner, K. R. & Curtin, J.J. (in prep)Moberg, C.A.  & Curtin , J.J. (2009). Journal of Abnormal Psychology, 118(2),         335-347.This work was supported by a grant  to John Curtin from NIAAA (R01 AA15384), an NRSA to Christine Moberg from NIAAA, and travel support from Guze Symposium.

Alcohol effects on affective response during variable and fixed duration threat

http://digitalcommons.wustl.edu/cgi/viewcontent.cgi?article=1018&context=guzeposter2010

Alcohol effects on affective response during variable and fixed duration threat

Abstract

Similar works

Full text

Available Versions

Digital Commons@Becker