Table 1.
Summary of literature investigating sex differences or female effects of stress on alcohol-related behaviors.
| Sex | Subjects | Stressor | Age (Tx) | Age (Test) | Measures | Outcome (group) | Citation |
|---|---|---|---|---|---|---|---|
| Mouse | |||||||
| Behavior | |||||||
| F=M | HAP | repeated RS | Adult | Adult | EtOH drinking ASR |
↑ drinking (RS M), ↓ drinking (RS F); ND ASR | Chester et al., 2005 |
| F=M | B6 | Various | Adult | Adult | EtOH drinking hormone levels |
↑ drinking (predator odor, F>M); ↓ drinking (other stressors); ↑ CORT (F>M) | Cozzoli et al., 2014 |
| F=M | SW | Long/short MD | Neonatal (p2–14) | Adult | EtOH LMA Hormone levels |
↑ LMA (long MD F) ↑ CORT (F>M baseline; M>F post-EtOH) |
Kawakami et al., 2007 |
| F=M | KM | Footshock (acute, chronic) | Adol (p26) Adult (p56) |
Adol Adult |
EtOH CPP | Chronic stress > baseline (Adol); stress = baseline (Adult); ND by sex | Song et al., 2007 |
| F=M | WSC | RS | Adult | Adult | EtOH drinking | ND drinking (RS) ↑ drinking (F>M) |
Tambour et al., 2008 |
| F=M | B6/129 | UCMS | Adult | Adult (CA; IA) | EtOH drinking | ↑ drinking, LMA (UCMS M); ↑ drinking (F>M) | Quadir et al., 2017 |
| Rat | |||||||
| Molecular/Electrophysiological | |||||||
| M=F | SD | SS | Adult | Adult | CRF1 IP CRF1 internalization |
↑ Gs coupling, all females (HC/SS±OVX), SS males male SS ↑, female SS ↓ |
Bangasser et al., 2010 |
| M=F | SD | acute CRF on slice SS |
Adult | Adult | LC activity | LC activity F>M SS ↑ LC activity M not F |
Curtis et al., 2006 |
| F=M | Wi | SBSA | Adol (P28–42) | CeA CRF-IR | CRF-IR M>F; SBSA ↓ CRF-IR (M & F) | Karanikas et al. 2013 | |
| F=M | Wi, msP | EtOH (acute) CB1 Ant. (acute) |
CeM EPSP amplitude local stimulation) | EtOH ↓ EPSP (Wi M/F, msP M); CB1 Ant ↓ EPSP (Wi M, msP M/F); CB1 Ant ┤EtOH (Wi F); CB1 Ant ↑ EtOH (msP F) | Kirson et al., 2017 | ||
| F>M F=M |
Wi | EtOH (acute) CORT (acute) |
Adult | Adult | CeL and CeM EPSP amplitude (BLA stimulation) | EtOH ↓ EPSP (M>F) CeL: CORT ↓ EPSP (F only) proe CeM EtOH ↑ EPSP |
Logrip et al. 2017 |
| F=M | LE | CIE + WD | Adult | Adult | EPM, BLA EPSC amplitude (M/L stimulation) | ↑ ALB (M>F); ↓ PPR (M>F, M stimulation); ↑ EPSC (M>F, L stimulation | Morales et al. 2018 |
| F=M | SD | EtOH (0–3 g/kg) puberty |
Pre/peri/post | Adult | Hormone levels | ↑ ACTH, CORT (F, GDX M > M; emerged peripuberty) | Ogilvie & Rivier, 1996 |
| F=M | SD | 14d EtOH LD SS |
Adult | Adult | Hormone levels CeA cFos-IR |
LD ↑ CORT (M only); SS ↓ CORT (LD Fem only) LD ↑ cFos (F only); SS ↑ cFos in CRF neurons (LD M only) |
Retson et al. 2015 |
| F=M | EtOH (0.2–1.8 g/kg) | Adult | Adult | Hormone levels | ↑ ACTH, CORT (F>M; pro/est F > di F) | Rivier, 1993 | |
| F=M | SD | FS | Adult | Adult | Hormone levels | ↑ ACTH, CORT (F>M) | Rivier, 1999 |
| Behavior | |||||||
| F=M | Wi | EtOH (2.5 g/kg)+ MD ± SI or CORT manipulation |
Neonatal (p15) | Neonatal (p15) | EtOH LMA | ↑ LMA (MD ± SI, CORT manipulation; ND by sex) | Arias et al., 2010 |
| F=M | SD | EtOH (2.5 g/kg) SI |
Neonatal | Weanling (p15–18) | EtOH LMA (p21) | ND LMA | Arias et al., 2012 |
| F=M | SD | Chronic CORT | Adol (p30–50) | Adult (p90+) | EtOH drinking; Cue/YOH REINSTM | ↑ drinking, cue REINST (CORT F>H2O F>M); ↑ REINST (F>M; cue+YOH> cue or YOH) | Bertholomey et al., 2016 |
| F=M | SD; GDX ±E2/T |
YOH | Adult | Adult | EtOH drinking; Cue/YOH REINSTM | ↑ drinking (F>M; E2>T); ↑ REINST (F>M; ND E2/T) | Bertholomey et al., 2017 |
| F | LE | SI | Adol (p30–72) | Adult (p100+) | EtOH drinking ALB |
transient ↑ drinking (SI) ND ALB |
Butler et al., 2014 |
| M=F | LE | CIE | Adult | Adult | IA2BC, CB1 Ant | CIE ↑ IA2BC (M only); CB1 Ant ↓ IA2BC (M>F) | Morales et al. 2015 |
| F=M | SD | MD | Neonatal (p1–13) | Neonatal (p14–15) | EtOH CPP, LMA | ND EtOH CPP (MD) ↑ LMA (all; >2.0 g/kg) ND by sex |
Pautassi et al., 2012 |
| F=M | Wi | Single, long MD | Neonatal (p9) | Adol (p28–50) | EtOH drinking+ WD ± RS |
WD+RS (F>M) ↑ drinking (MD+RS) |
Peñasco et al., 2015) |
| F | Wi | Long/short MD | Neonatal (p1–21) | Adult | EtOH drinking ± RS |
ND drinking acquisition ↑ drinking (RS) |
Roman et al., 2004 |
| F=M | LE | SI, social instability | Adol (p30–46) | Late Adol/Adult | EtOH drinking ALB, hormone levels |
↑ drinking, ALB, ND CORT (male social instability); ND drinking, ALB, ↓ CORT (SI F) | Roekner et al., 2017 |
| F=M | Wi | Repeated RS | Adol (p30–34) Adult (p70–74) |
Adol (p30–34) Adult (p70–74) |
EtOH drinking ALB | ↑ drinking, ALB (adol RS F) ↓ drinking (RS M, adult F) |
Wille-Bille et al., 2017 |
| Human | |||||||
| F=M | AD± PTSD | Cold pressor stress test | Adult | Adult | Subjective/hormonal stress rating | ↑ subjective stress ╪ ACTH (AD±PTSD) ↓ basal, greater ↔ ACTH (F vs. M) |
Brady et al., 2006 |
| M>F | CS+AA; TS | Stress Imagery Alcohol Cue |
Adult | Adult | Drug craving Emotional response Hormone levels |
↑ craving, anxiety, ACTH, CORT (more frequent users) | Fox et al., 2005 |
| M>F | AD; TS | Stress Imagery Alcohol Cue |
Adult | Adult | Alcohol craving Emotional response Hormone levels |
↑ craving, negative emotions (stress, cue) ↑ CORT (cue) |
Fox et al., 2007 |
| F=M | AD+CA; TS | Stress Imagery Alcohol Cue |
Adult | Adult | Alcohol craving Hormone levels |
↑ craving (cue M) ↑ ACTH, CORT (stress F) ╪ ACTH, CORT (stress, cue M) |
Fox et al., 2009 |
| M>F | AD; TS; ABST | Stress Imagery Alcohol Cue |
Adult | Adult | Alcohol craving Emotional response Hormone levels |
↑ craving, negative emotions (stress, cue) ╪ ACTH, CORT (stress, cue) |
Sinha et al., 2009 |
| M>F | AD; TS | Stress Imagery Alcohol Cue Prazosin |
Adult | Adult | Alcohol craving Emotional response Hormone levels |
↑ craving, anxiety; ↔ ACTH, CORT (stress, cue); Prazosin ↔ these effects | Fox et al., 2012 |
| M>F | Human (AD; TS; ABST) | Stress Imagery Alcohol Cue |
Adult | Adult | Alcohol craving Latency to Relapse Hormone levels 90-day follow-up |
↑ craving and baseline CORT ↓ time to relapse |
Sinha et al., 2011 |
| M>F | AD | GR Ant | Adult | Adult | Alcohol craving, | GR Ant ↓ craving, drinking | Vendruscolo et al., 2015 |
Effects indicators: ↑increase, ↓ decrease, ╪ blunted, ┤ blockade, ND no difference
Abbreviations: Sex: M = male; F = female; Species/Rodent lines: Ms = mouse; B6 = C57BL/6; HAP = high alcohol-preferring; KM = Kunming; LE = Long-Evans; SD = Sprague-Dawley; SW = Swiss Webster; Wi = Wistar; WSC = withdrawal seizure control, Estrous cycle indicators: pro = proestrus, est = estrus, di = diestrus; Experimental terms: AA = alcohol abusing; ABST = abstinent; ACTH = adrenocorticotropic hormone; AD = alcohol dependent; ALB = anxiety-like behavior; ant = antagonist; ASR = acoustic startle response; BLA = basolateral amygdala; CIE = chronic intermittent ethanol vapor; CA= cocaine abusing; CD = cocaine dependent; CeA = central amygdala; CeL = lateral CeA; CeM = medial CeA; CORT = corticosterone (rodent)/cortisol (human); CPP = conditioned place preference; CRF = corticotropin-releasing factor; EPSP/C = excitatory postsynaptic potential/current; EPM = elevated plus maze; EtOH = ethanol (alcohol); E2 = estradiol; FC = fear conditioning; FS = Footshock; GDX = gonadectomized; g/kg = grams of ethanol per kilogram of body weight; GR = glucocorticoid receptor; IA2BC = intermittent access to 2-bottle choice; IR = immunoreactivity; LC = locus coeruleus; LD = alcohol-containing liquid diet; LMA = locomotor activity; MD = maternal deprivation/separation; mPFC = medial prefrontal cortex; PTSD = post-traumatic stress disorder; p# = postnatal day; SA = self-administration; SBSA = sweetened EtOH binge-like self-administration; SI = social isolation; SS = swim stress; T = testosterone; TS = treatment seeking; REINST = reinstatement; RS = restraint stress; UCMS = unpredictable chronic mild stress; WD = withdrawal; YOH = yohimbine;