Table 1.
Results and details of recent animal studies investigating AAE.
| Reference | Species | Sex | Dose, Route of Administration | Age of Exposure (PND) | Age at Test(s) (PND) | Behavior Category | Behavior Test(s) | Behavioral Results | Brain Region(s) | Results |
|---|---|---|---|---|---|---|---|---|---|---|
| Maldonado-Devincci & Kirstein [32] | Rat | M, F | .75, 1.5 g/kg, i.p | 30–50 | 65–80 | Drug Taking | Oral s-a | ↑ alcohol s-a in adolescent female rats given 1.5 g/kg alcohol exposure | ||
| Maldonado-Devincci et al. [33] | Mouse | M, F | Vapor exposures, 10 liters/min | 28–42 | 49–81, 70–102 | -Drug Taking |
-2 BC -OF |
-↑ alcohol s-a in males after short abstinence -↓ alcohol s-a in females after long abstinence |
||
| Lee et al. [40] | Mouse | M | Oral s-a, 5–40% | 28–41 | 70 | Depression | FST, sucrose preference test | ↑ DLB | NAc shell, CeA | ↑ mGlu1express in shell |
| Lee et al. [41] | Mouse | M | Oral s-a, 5–40% | 28–41 | 70 |
-Anxiety -Depression |
-LDB -FST |
↑ ALB and DLB | ||
| Sampedro-Piquero et al. [42] | Mouse | M | Oral s-a, 15% | 21–52 | 58, 78 | Anxiety | EZM | ↑ ALB | PFC, Hippocampus, CeA, hypothalamus, BLA |
-↓ BDNF Expression -↑ GR density -↑ CRF density |
| Van Hees et al. [43] | Mouse | M, F | Oral s-a, 20% | 29–40 | 43, 80 |
-Anxiety -Depression -Drug Taking |
-OF, EPM -FST -2 BC |
-↑ Increased ALB, DLB, and alcohol consumption at adulthood | PFC | No change in microglia activation |
| Brancato et al. [42] | Rat | Oral s-a, 25% | 35–54 | 64 |
-Anxiety -Depression |
-Social Interaction Task -FST |
-↑ ALB -↑ DLB |
PVN, NaC |
-↑ CRF expression -↑ D1 expression -↓ D2 expression |
|
| Pandey et al. [50] | Rat | M | 2 g/kg, 20% i.p. | 28–41 | 92 |
-Anxiety -Drug Taking |
-EPM -Alcohol Consumption |
-↑ ALB -↑ alcohol consumption |
Amygdala |
-↑ HDAC activity -↓ BDNF and Arc expression |
| Bohnsack et al. [52] | Rat | M | 2 g/kg, 20% i.p. | 28–41 | 120 |
-Anxiety -Drug Taking |
-EPM, LDB -2 BC |
-Impaired performance -↑ alcohol consumption |
CeA | ↓ Arc mRNA expression |
| Lawson et al. [54] | Mouse | M, F | Oral s-a, 20% | 39.5–44.5 | 68.5 | Memory | Conditioned freezing | ↓ extinction recall | PL | ↓ dendritic complexity |
| Kyzar et al. [51] | Rat | M | 2 g/kg | 28–41 | 100 | Anxiety | EPM, LDB | ↑ ALB | CeA | ↓ Arc enhancer ↓ Arc mRNA expression RNA expression |
| Salling et al. [55] | Mouse | M | Oral s-a, 15% | 30–60 | 64–80 | Working memory | Nonmatch to Sample | Impaired performance | PL | -Hyperpolarization of resting membrane potential |
| Fernandes et al. [56] | Rat | F | Intragastric administration 3 g/kg, 20% | 35, 35–58, 35–86 | 35, 49, 58, 72, 86, 100 |
-Anxiety -Working memory |
-OF, EPM -NOR |
↑ ALB Impaired performance | Hippocampus |
-↓ BDNF expression -↑ GFAP level |
| Jury et al. [58] | Mouse | M | Vapor Inhalation + IP injection 19–22 mg EtOH/I + 1.5 g/kg, 20% | 35–63 | 64 | IL, BLA |
-↓ IL neuronal spine density -↑ head width of BLA spines |
|||
| Galaj et al. [59] | Rat | M | Intragastric administration 4 g/kg | 28–45 | 47, 66 | PL |
-Modified L5 PNs -↑ intrinsic excitability of L5 PNs |
|||
| Silva-Gotay et al. [60] | Rat | M, F | Oral s-a 10% | 28–42 | 43 | mPFC |
-↑ gene expression of pro-inflammatory factors -↑ in TLR4 gene expression in males |
|||
| Broadwater et al. [61] | Rat | M | Intragastric administration 5 g/kg, 25% | 25–54 | 78.5 | Frontolimibic regions | ↓ resting-state connectivity between PFC and subregions and PFC-striatal regions | |||
| Tavares et al. [62] | Rat | M, F | Oral s-a, 10% | 28–42 | 43 | CG1 |
-↓ myelinated fiber density in males -No effect in females |
|||
| Vetreno & Crews [64] | Rat | M | Intragastric administration 5 g/kg, 20% | 25–55 | 56, 80, 220 |
-Working memory -Anxiety |
-NOR -OF |
-Impaired performance -↑ ALB |
DG |
-↓ neurogenesis -↑ cell death |
| Mulholland et al. [66] | Rat | M | Intragastric administration 5 g/kg, 35% | 30–46 | 70 | Hippocampus |
-↓ dendritic spine density -Altered dendritic spine morphology |
|||
| Healey et al. [68] | Rat | M, F | Intragastric administration 5 g/kg, 35% | 30–46 | 70 | CA1 |
-↓ dendritic spine density -Altered dendritic spine morphology |
|||
| Risher et al. [70] | Rat | M | Intragastric administration 5 g/kg, 35% | 30–46 | 47 | Hippocampus | ↑ astrocyte reactivity | |||
| Nwachukwu et al. [71] | Rat | M, F | Intragastric administration 5 g/kg, 35% | 31–46 | 77 | Hippocampus |
-↑ astrocyte activation -↑ in GFAP+ cells |
|||
| Healey et al. [72] | Rat | M | Intragastric administration 5 g/kg, 35% | 31–46 | 74 | Hippocampus | ↓ astrocytic-synaptic contact | |||
| Swartzwelder et al. [73] | Rat | M | Intragastric administration 5 g/kg, 35% | 30–46 | 70–75 | Hippocampus | Alterations in GluN2B proteome | |||
| Swartzwelder et al. [74] | Rat | M | Intragastric administration 5 g/kg, 35% | 30–46 | 71 | CA1 | ↑ NMDA receptor-mediated evoked EPSCs | |||
| Walker et al. [77] | Rat | M | Intragastric administration 5 g/kg, 35% | 30–45 | 46, 72 | VO-PFC |
-↑ intermediate dendritic spines -↓ in mature dendritic spines |
|||
| Peng & Nixon [80] | Rat | M | Intragastric administration 5 g/kg, 35% | 34–38 | 38, 40, 45, 52 | Hippocampus, entorhinal cortex | ↑ microglia activation | |||
| Hu et al. [81] | Mouse | M | Intragastric administration 3.5 g/kg, 25% | 28–42 | 63 | Depression | FST, Sucrose preference test | ↑ DLB | DG | Apoptosis and dystrophy of microglia |
| Marshall et al. [82] | Rat | M | Intragastric administration 5 g/kg, 25% (titrated) | 35–39 | 39 | DG |
-↑ microglial dystrophy -↓ BDNF expression |
|||
| Agoglia et al. [87] | Mouse | M | Oral s-a, 20% | 28–42 | 36–42 | CB1 receptors | ↓ alcohol s-a following inhibition of CB1 receptors | |||
| Sánchez-Marín et al. [89] | Rat | M | Oral s-a, 10% | 35–37, 39 | 37, 39 | Hippocampus, perirhinal cortex, entorhinal cortex |
-↓ number of microglia -↑ microglia dystrophy -↓ BDNF expression |
|||
| Sánchez-Marín et al. [89] | Rat | M | Intragastric administration, 3 g/kg, 25% | 31–55 | 62 | mPFC, amygdala, hippocampus |
-↑ mRNA expression of EC signaling -↑ neuroinflammation |
|||
| Sánchez-Marín et al. [44] | Rat | M | 3 g/kg, 20%, i.p. | 31–55 | 62–70 |
-Anxiety -Working memory |
-OF, EPM -NOR |
-↑ ALB -Impaired performance |
mPFC, amygdala, striatum |
-↑ CB1 and CB2 protein expression -↑ CRF receptor protein expression -Region-specific changes in expression of cannabinoid synthetic enzymes |
| Peñasco et al. [90] | Mouse | M | Oral s-a, 20% | 32–56 | 67 | Cognition | NOR | Impaired performance | Hippocampus |
-↓ CB1 expression -Impaired CB1 dependent LTD |
Note: PND post-natal days, M male, F female, s-a self-administration, i.p intraperitoneal, EZM elevated zero maze, FST forced swim test, EPM elevated plus maze, LDB light dark box, 2 BC 2-bottle choice, OF open field, NOR novel object recognition, ALB anxiety-like behavior, DLB depression-like behavior, VO-PFC ventral orbital-PFC, EPSC excitatory postsynaptic current, empty spaces indicate information that was not relevant to study or was not specified.