Table 2.
Results and details of recent animal studies investigating ACE.
| Reference | Species | Sex | Route of Administration, Dose | Age of Exposure (PND) | Age at Test(s) (PND) | Behavior Category | Behavior Test(s) | Behavioral Results | Brain Region(s) | Results |
|---|---|---|---|---|---|---|---|---|---|---|
| Lee et al. [118] | Mouse | M, F | 5 mg/kg, i.p. | 30–44 | 70 | Alteration in genes associated with microglia homeostasis and immunity | ||||
| Wan et al. [119] | Mouse | M | 2 mg/kg, i.p. (WIN) | 33–45 | 70-71 | mPFC, hippocampus, NAc | ↑ Iba1 expression in mPFC and NAc following administration of lipopolysaccharide | |||
| Renard et al. [125] | Rat | M | 2.5, 5, 10 mg/kg, i.p. (2x daily) | 35–46 | 75 |
-Working memory -Anxiety |
-NOR -LDB, OF |
-Impaired working memory -↑ ALB |
PFC, VTA |
-↓ GAD67 expression in mPFC -↑mPFC PN firing rate -↑ VTA dopamine neuron firing |
| Gabaglio et al. [128] | Rat | F | 2.5, 5, 10 mg/kg, i.p. (2x daily) | 35–45 | 75 |
-Working memory -Depression -Anxiety |
-NOR -FST, Sucrose intake -EPM |
-Impaired working memory -↑ DLB -↑ALB |
PFC | ↓ GAD67 expression |
| Renard et al. [130] | Rat | 2.5, 5, 10 mg/kg, i.p. (2x daily) | 35–45 | 75 |
-Anxiety -Fear |
-EPM, OF -Prepulse startle inhibition |
-↑ ALB - ↑ prepulse inhibition |
VTA | ↑ VTA DA neuron firing | |
| Scherma et al. [131] | Rat | M | 2.5, 5, 10 mg/kg, i.p. (2x daily) | 45–55 | 70 |
-Drug taking -Anxiety -Fear -Depression |
- WIN s-a -EPM -Prepulse startle inhibition -Sucrose preference test |
-↑ s-a -No changes in ALB, DLB, or fear |
VTA, NaC shell |
-↓ WIN-induced DA activity in VTA -↑ WIN-induced DA activity in NAc shell |
| Kruse et al. [133] | Rat | M,F | THC gelatin consumption 1.0, 1.5, and 2.0 mg/15 ml | 25–58 | 93 | Reward learning | Pavlovian conditioned approach | -↑ Pavlovian conditioned approach in males | VTA | ↓ of CB1 expressing VGLUT1 synaptic terminals in males |
| Friend et al. [263] | Mouse | M | 10 mg/kg, i.p. | 14.5–23.5 | 23.5 | VTA | Interference of LTD in GABAergic cells | |||
| Zamberletti et al. [264] | Rat | M | 2.5, 5, 10 mg/kg, i.p. (2x daily) | 35–45 | 75 |
-Memory -Depression |
-NOR -FST |
-Impaired performance -No effect |
Hippocampus, PFC |
-↑ GluN2B, GluA1, and GluA2 expression in hippocampus -↑ astrocytic neuroinflammation in PFC |
| Le et al. [134] | Rat, Mouse | M, F | 5 mg/kg, i.p. | 30–43 | 80 | Memory | Serial “what” task, 2-odor discrimination, OLM | Impaired Performance | Hippocampus | ↓ potentiation of S-C projection to CA1 in females only |
| Zuo et al. [136] | Mouse | M, F | 10 mg/kg, i.p. | 28–48 | 70 |
-Anxiety -Memory |
-EPM -Six different object test |
-No effect -Impaired working memory in females |
Amygdala, DMS | Larger number of DEGs in females |
| Orihuel et al. [138] | Rat | M, F | 3 mg/kg, i.p. | 28–48 (every other day) | 90 | -Reward learning | -Pavlovian conditioned approach |
-Increased goal-tracking -Increased PIT |
NAc shell | Sex-specific changes in transcriptome profile |
| Chen & Mackie [141] | Mouse | M, F | I.P. injection 10 ml/kg | 28–49 | 65 |
-Working memory -Anxiety |
-Delayed alternation T maze -EPM |
-Impaired working memory -No effect |
||
| Withey et al. [142] | Squirrel Monkey | M | Intramuscular Injection, 1 mg/kg | 27–31 months | NS | Cognition | Discrimination leaning, discrimination reversal | Impaired performance | ||
| Verrico et al. [143] | Rhesus Monkey | M | Intravenous s-a 15–240 μg/kg | 28.6–33.6 months | 29 months | Working memory | Delayed match to sample | Impaired performance | ||
| Prini et al. [155] | Rat | F | I.P. Injection 2.5, 5, 10 mg/kg (2x daily) | 35–45 | 45, 46, 47 | Hippocampus, NAc, PFC | Transcriptional repression | |||
| Prini et al. [156] | Rat | F | 2.5, 5, 10 mg/kg, i.p. (2x daily) | 35–45 | 45, 46, 47, 70 | Working memory | NOR | Impaired Performance | PFC |
-Histone modification -↑ H3K9me3 |
| Miller et al. [157] | Rat | M | 1.5 mg/kg, i.p. | 28–48 (every third day) | 49, 63 | PL | ↑ dendritic spine pruning, altered gene networks | |||
| Leishman et al. [158] | Mouse | F | 3 mg/kg, i.p. | 35, 50 | 35, 50 | Hippocampus | Changes in transcriptome | |||
| Stringfield & Torregrossa [22] | Rat | M, F | 3, 10, 30, 100 μg/kg/infusion | 32–51 | 85 | Working memory | Delayed match to sample | Impaired performance in females, improved performance in males | PFC, DH, VTA | ↓ in CB1, GABA, and glutamate receptor protein |
| Kirschmann et al. [161] | Rat | F |
-WIN intravenous s-a, 0.0125 mg/kg/infusion -WIN, 0.2, 1.2 mg/kg, i.p. |
-34–59 -34–53 |
60, 54 | Working memory | NOR, Delayed match to sample |
-No effect of s-a -Improved working memory |
||
| Kirschmann et al. [162] | Rat | M |
-WIN intravenous s-a, 0.0125 mg/kg/infusion -WIN, 0.2 mg/kg, i.p. |
38–49 | 110 | Working memory | NOR, Delayed match to sample | Improved performance | PFC | ↑ in expression of proteins regulating GABAergic and glutamatergic signaling |
| Bruijnzeel et al. [163] | Rat | M, F |
-Cannabis smoke exposure, 5.6% THC, 0% CBD -2.5, 5, 10 mg/kg, i.p. (2x daily) |
-29–49 -35–45 |
70 |
-Anxiety -Depression -Working memory |
-OF, EPM -Sucrose preference, FST -NOR |
No effect | ||
| Hernandez et al. [164] | Rat | M | Cannabis smoke exposure 5.6% THC, 0% CBD | 29–49 | 70 |
-Anxiety -Addiction-like behavior |
-EPM, OF -Progressive ratio, set shift task |
No effect |
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, OLM object location memory, ALB anxiety-like behavior, DLB depression-like behavior, PIT Pavlovian instrumental transfer, empty spaces indicate information that was not relevant to study or was not specified.