Table 1.
Methodological Description of Reviewed Caffeine Studies
| Authors | Subjects | Design | Timing of administration | Method of administration | Dosage | Behavioral test |
|---|---|---|---|---|---|---|
| Baldwin and File26 | Male hooded Listar rats; n = 7–15 | Between-groups, controlled design | 30 min before testing | IP | 20, 40 mg/kga | Social interaction test |
| Baldwin et al.8 | Male hooded Listar rats; n = NA | Between-groups, controlled design | 30 min before testing | IP | 40 mg/kga | Social interaction test Elevated plus maze Punished-drinking test |
| Bert et al.13 | Male, female Sprague Dawley and Wistar rats; n = 9–10 | Controlled, mixed research design | 30 min before testing | IP | 50 mg/kga | Free exploration test Elevated plus maze |
| Bradley et al.34 | Male, female Mongolian gerbils, seizure-resistant strain; n = 10–12 | Between-groups, controlled design | 30 min before testing | IP | 0.5–30 mg/kga | Black-white box |
| Braun et al.47 | Male, female Sprague Dawley rats; n = 7 | Between-groups, controlled design | 30 min before testing | Subcutaneous injection | 100 mga | Elevated plus maze Elevated zero maze |
| Cachat et al.19 | Male, female wild-type zebrafish; n = NA | Between-groups, controlled design | 1-week exposure, 12-h washout before testing | Tank water exposure | 50 mg/La | Novel tank test |
| Carvalho-Netto and Nunes-de-Souza33 | Male Swiss mice; n = 10–12 | Controlled, mixed research design | 30 min before testing | IP | 10, 30 mg/kga | Elevated T-maze |
| Celec and Behuliak28 | Male Wistar rats; n = NA | Between-groups, controlled design | 3-month exposure before testing | Free access to caffeinated drinking water | 30–60 mg/kg/day (Approx.) | Light/dark box |
| Egan et al.7 | Male, female wild-type, long-fin, leopard, and albino zebrafish; n = 21 | Between-groups, controlled design | 5-min exposure before testing | Exposure in beaker water | 100 mg/L in 3-L beakera | Novel tank diving test |
| El Yacoubi et al.16 | Male Swiss albino CD1 mice, A2A receptor knockout mice and wild-type controls; n = 8–16 | Between-groups, controlled design | Acute: 30 min before testing Chronic: 1-, 8-, 60-day exposure before testing |
Acute: IP Chronic: free access to caffeinated drinking water |
Acute: 12.5–100 mg/kg Chronic: 4.1–5.9 mL/mouse day (Approx.)a |
Elevated plus maze Light/dark test |
| File37 | Male hooded Listar rats; n = 23 | Controlled, mixed research design | Daily injections on days 1–7; testing occurred on days 35–36 | Subcutaneous injection | 15–30 mg/kga | Social interaction test Elevated plus maze |
| Garcia et al.5 | Male Wistar-derived rats; n = 11–12 | Between-groups, controlled design | 30 min before testing | IP | 10, 30 mg/kga | Elevated plus maze |
| Gulick and Gould (2009)43 | Male C57BL/6J mice; n = 6–10 | Between-groups, controlled design | 30 min before training; testing occurred 24 h later | IP | 5–40 mg/kga | Plus maze discrimination avoidance task |
| Hughes11 | Male, female Piebald Virol Glaxo/C rats; n = 10 | Between-groups, controlled design | 10-day exposure day 45–55; testing occurred day 120 | Free access to caffeinated drinking water | 20–30 mg/kg (Approx.) | Light/dark box Open field test |
| Jain et al. (1995)44 | Male ICR or MF1 rats; n = 10 | Between-groups, controlled design | 15 min before testing | IP | 15–60 mg/kga | Elevated plus maze |
| Jain et al.14 | Male Sprague Dawley rats; n = 6 | Between-groups, controlled design | 30 min before testing | IP | 5–100 mg/kga | Elevated plus maze |
| Khor et al.22 | Male wild-type zebrafish; n = 12–20 | Between-groups, controlled design | 24-h exposure followed by 24 h before testing | Exposure in Petri dish | 5, 50 mg/La | Novel tank diving test |
| Kulkarni et al.6 | Male, female Laca mice; n = 6 | Between-groups, controlled design | 30 min before testing | NA | 8–60 mg/kga | Elevated plus maze Elevated zero maze |
| Kurt et al.41 | Male, female ICR rats; n = 8 | Between-groups, controlled design | 30 min before testing | IP | 30 mg/kga | Elevated plus maze |
| Lapin (1998)45 | Male Albino SHR mice; n = 32 | Between-groups, controlled design | 15 min before testing | IP | 50 mg/kga | Dark/light chamber |
| Lister12 | Male NIH Swiss mice; n = 7–11 | Between-groups, controlled design | 25 min before testing | IP | 15–60 mg/kga | Elevated plus maze |
| Maximino et al.23 | Unsexed wild-type zebrafish; n = 10 | Between-groups, controlled design | 15 min before testing | Injection | 100 mg/kga | Scototaxis test |
| Maximino et al.2 | Unsexed wild-type zebrafish; n = 10 | Between-groups, controlled design | 15 min before testing | Injection | 1–100 mg/kga | Scototaxis test |
| Noschang et al.3 | Male, female Wistar rats; n = 7–13 | Between-groups, controlled design | 50–60-day exposure before testing | Free access to caffeinated drinking water | 40, 108 mg/kg/day (Approx.) | Elevated plus maze Open field test |
| Oettinger et al.21 | Female Wistar; rats; n = 15 | Controlled, mixed research design | 15 min before testing | IP | 8–32 mg/kg | Tunnel maze with open field |
| Park et al.4 | Male ICR mice, male Wistar rats; n = 5–9 | Between-groups, controlled design | 30 min before testing | IP | 25 mg/kga | Elevated plus maze Open field test |
| Pechlivanova et al.27 | Male Wistar rats; n = 10 | Between-groups, controlled design | 4-week exposure before testing | Oral gavage | 8 mg/kg/daya | Elevated plus maze Open field test |
| Prediger et al.17 | Male Swiss albino mice; n = 8 | Between-groups, controlled design | 30 min before testing | IP | 10, 30 mg/kga | Elevated plus maze |
| Richendrfer et al.24 | Wild-type zebrafish (Sex NA); n = 35–48 | Controlled, mixed research design | 2 h before testing and 1 h during testing | Caffeinated egg water exposure | 10–100 mg/La | Thigmotaxis test with five-fish behavioral assay |
| Ruiz-Medina et al.39 | Male CD1 mice; n = 10 | Controlled, mixed research design | 7–21-day exposure before testing | IP | 10–30 mg/kga | Dark/light box test |
| Sanday et al.40 | Swiss male mice; n = 10 | Controlled, mixed research design | 30 min before either pretraining, testing or both | IP | 20 mg/kg | Plus maze discrimination avoidance task Inhibitory avoidance task |
| Silva and Frussa-Filho46 | Male Swiss EPM-M1 mice; n = 10 | Controlled, mixed research design | 30 min before conditioning, testing occurred 24 h later | IP | 20 mg/kga | Plus maze discrimination task |
| Schnörr et al.9 | Wild-type zebrafish (sex NA); n = 25 | Between-groups, controlled design | 10-min exposure during testing | Caffeinated egg water exposure | 50 mg/La | Thigmotxis test with 24-well assay |
| Steenbergen et al.25 | Wild-type zebrafish (sex NA); n = 27 | Between-groups, controlled design | 7 min exposure, followed by 3-s washout before testing | Caffeinated egg water exposure | 85 mg/La | Light/dark preference test |
| Vila-Luna et al.20 | Male Wistar rats; n = 13 | Controlled, mixed research design | 6-month exposure, followed by 2-week washout before testing | Free access to caffeinated water | 5 mg/kg/day | Elevated plus maze |
| Vitale et al.15 | Male Wistar rat; n = 8 | Between-groups, controlled design | 30 min before testing | IP | 20 mg/kga | Defensive burying test |
Studies are presented in the alphabetical order of authorship. Doses listed as ranges if more than two were used.
a
Other drugs evaluated in study in addition to caffeine.
IP, intraperitoneal injection; n, number of subjects in caffeine group; NA, information not available.