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. 2023 Oct 6;13:313. doi: 10.1038/s41398-023-02590-4

Table 3.

Results and details of recent animal studies investigating ANE.

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
Corongiu et al. [189] Rat M 0.4 mg/kg s.c. 35, 42, 49 25, 42, 49 NAc shell. DLS

-↑ extracellular DA

- No effect

Cardenas & Loftipour [181] Rat M,F 20 µg/kg/.1 ml, intravenous 28–31 32–36 Drug taking Meth s-a ↑ meth s-a in males, but not females
Locker et al. [182] Mouse F Oral s-a, 200 µg/ml 35–41 42–44 Drug taking Alcohol s-a ↑ alcohol s-a Frontal cortex ↑ nAChR density
Cardenas et al. [183] Rat M,F 30 µg/kg/.1 ml, intravenous 28–31 32 Drug taking Cocaine and fentanyl s-a ↑ drug s-a
Reed & Izenwasser al. [184] Rat M 0.4 mg.kg i.p. 30–36 39–45 Drug Taking Cocaine s-a ↑ cocaine s-a
Lenoir et al. [190] Rat M, F 0.001-1 mg/kg i.p. 35–37 35–37, 38 Conditioned reward CPP ↑ CPP in adolescents than adults NAc, caudate putamen ↑ nAChR density
Cao et al. [191] Rat M, F 30 µg/kg/100 µl intravenous 28, 38 28, 38 Drug reward Locomotor activity ↑ locomotor activity in adolescents than adults
Renda et al. [192] Mouse M 200 µg/ml Oral s-a 44.4–49.5, 54–59, 60–65 44.4–49.5, 54–59, 60–65 Drug consumption 2 BC ↑ consumption in adolescents than adults VTA ↑ α4* NACHR in adolescent than adults, correlation between nicotine consume and α4* NACHR expression
Schassburger et al. [194] Rat M,F 3, 10, 30 µg/kg/infusion, intravenous s-a 30–46 30–46 Drug consumption Instrumental responding ↑ responding in adults than in adolescents
Weaver et al. [195] Rat M 0.32 mg/kg s.c. 29–42 64 Reward learning Instrumental responding for reward cue No impact of ANE on responding in adulthood
Jobson et al. [172] Rat M 0.4 mg/kg s.c., (3x daily) 35–44 76

-Anxiety

-Depression

-OF, LDB, sub-threshold fear memory

-FST,

-↑ ALB

-↑ DLB

VTA, PFC

-↑ firing of VTA and PFC DA neurons

-↓ PFC D1 protein expression

-↑ PFC pERK1-2 expression

Hudson et al. [198] Rat M 0.4 mg/kg s.c. 35–44 (3x daily) 75

-Anxiety

-Depression

-OF, LDB

-FST, Sucrose Preference

-↑ ALB

-↓ DLB

NAc shell

-↑ pERK1-2 expression

-↑ GSK-3 phosphorylation

-↓ D1 expression

-Altered MSN firing rate

Counotte et al. [205] Rat M 0.4 mg/kg s.c. 34–43 (3x daily) 78 Attention 5-choice serial reaction time task Impaired performance PFC ↓ mGluR2 protein expression and function
Xue et al. [220] Rat M, F 0.03, 0.1, 0.1, mg/kg, s.c. 50–54 50–54 Reward Intracranial self-stimulation ↓ reward threshold in both sexes, greater reduction in females
Chellian et al. [221] Rat M, F

-NRC 200 (0.07 mg/cigarette)/NRC 600 (0.84 mg/cig) smoke exposure

- 0.3 mg/kg, s.c.

24–42 55 Drug taking Nicotine s-a ↑ s-a nicotine intake in females but not males
Goriounova & Mansvelder et al. [206] Rat 0.4 mg/kg s.c. 34–43 (3x daily) 46, 78 mPFC Altered spike-timed dependent plasticity
Holliday et al. [196] Mouse M 0.25 µl/hour s.c. osmotic pump 32–44 45, 74

-Anxiety

-Depression

-Cognition

-EPM

-FST

-Contextual fear conditioning

-↑ ALB

-↑ DLB

- Impaired contextual freezing

CA1 ↓ dendritic spine length and complexity
Gitik et al. [209] Mouse M 0.25 µl/hour s.c. osmotic pump 23, 38–35, 50 68, 80 Cognition Contextual fear conditioning ↓ contextual freezing Hippocampus Altered methylation of chromatin remodeling genes
Connor & Gould [207] Mouse M 12.6 mg/kg/day, s.c. osmotic pump 38, 38–68 70 Learning Trace fear conditioning ↓ fear learning Dorsal hippocampus ↓ BDNF expression
Linker et al. [216] Rat M, F 30 µg/kg/.1 ml intravenous 28–31 (2x daily) 32 Drug taking Cocaine s-a ↑ acquisition of cocaine s-a NAc, BLA -↑ in IBA+ cells and IBA1 expression

Note: PND post-natal days, M male, F female, NRC nicotine research cigarette, s-a self-administration, i.p intraperitoneal, s.c. subcutaneous, FST forced swim test, EPM elevated plus maze, LDB light dark box, 2 BC 2-bottle choice, OF open field, ALB anxiety-like behavior, DLB depression-like behavior, DLS dorsal lateral striatum, CPP conditioned place preference, empty spaces indicate information that was not relevant to study or was not specified.