Table 6.
Solitary behaviours in postnatally MDMA-treated rodents, compared with control rodents.
| Study | Species | Sexes | Sexes Combined or Separated | Sample Size | Singular/Chronic Dosing | Chronic Timing | Dose (mg/kg) | Route | Treatment Age (PD) | Testing Age (PD) | Temperature (°C) | Males | Females | Both | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Abad 2014 [191] | Rat | Males | NA | 16-24 | Chronic | Twice daily for 4 days | 20 | s.c. | 35 | 46 | 26 | More time spent in centre. | NA | NA | |||||||||||
| Ball 2011 [238] | Rat | Males | NA | 64 | Chronic | 2 daily for 5 consecutive days (6 hours apart) | 5 | i.p. | “Adult” (300-400g) | Same days | NA | Paired MDMA: increased locomotor activity (15 days post-injection). 100 days post-injection: only homecage-treated had hyperlocomotion. | NA | NA | |||||||||||
| Ball 2011 [238] | Rat | Males | NA | 63 | Singular | 15 or 100 days later | 2.5 | i.p. | “Adult” (300-400g) | Same day | NA | Hyperlocomotion in unpaired, 100 days post-injection = hyperlocomotion in paired, 15 days post-injection. 100 days post-injection: paired had higher stereotypy (at 15 days post-injection, higher than MDMA-treated unpaired). | NA | NA | |||||||||||
| Biezonski 2009 [239] | Rat | Males | NA | 16 | Chronic | Twice daily, 4 hours apart, every 5th day | 10 | s.c. | 35-60 | 67 | 23-24 | No effect. | NA | NA | |||||||||||
| Braida 2002 [240] | Rat | Males | NA | 40 | Chronic | Daily | 1, 2, 3, 4 | i.p. | 90 | 104 | 22 | 4 mg/kg: increased line crossings and stereotypy | NA | NA | |||||||||||
| Bull 2003 [133] | Rat | Males | NA | 24 | Chronic | Twice daily | 15 | i.p. | 28-30 | 28 | 21 | 15 mg/kg: higher sustained locomotion (controls: low decreasing locomotion), over 30 mins. Fewer rears, decreased to low plateau (controls: rearing progressively declines). Serotonin syndrome: reciprocal forepaw treading, lateral head weaving, flat body posture. | NA | NA | |||||||||||
| Bull 2004 [132] | Rat | Males | NA | 32 | Chronic | Each of 4 hours | 5 | i.p. | 28 | 84 | 21 | Sustained hyperlocomotion, fewer rearings. | NA | NA | |||||||||||
| Callaway 1990 [241] | Rat | Males | NA | 55 | Singular | NA | 0.3, 1, 3, 10 | s.c. | “Adult” (300-400g) | Same day | NA | 1, 3, 10 mg/kg: decreased exploration (holepokes, rearings). 10 mg/kg: increase of routes taken repetitively. 3, 10 mg/kg: increased sustained hyperlocomotion. Centre avoidance, direction alternation. | NA | NA | |||||||||||
| Callaway 1992 [242] | Rat | Males | NA | 32 | Chronic | 1-week intervals | 10, 30 microg. | i.c. | 300-400g | Same day | NA | Hyperactivity (30 microg. slightly later than 10 microg.). 30 microg.: hypolocomotion in 1st 10 mins., increased rearings. 10 microg.: decreased holepokes. Results dependent on cerebral area injected. | NA | NA | |||||||||||
| Clemens 2004 [217] | Rat | Males | NA | 63 | Chronic | 4 injections in 1 day, one every 2 hours | 2.5 | i.p. | 376g | Same time | 28 | Higher total locomotion. | NA | NA | |||||||||||
| Study | Species | Sexes | Sexes Combined or Separated | Sample Size | Singular/Chronic Dosing | Chronic Timing | Dose (mg/kg) | Route | Treatment Age (PD) | Testing Age (PD) | Temperature (°C) | Males | Females | Both | |||||||||||
| Clemens 2005 [218] | Rat | Females | NA | 56 | Chronic | Every 2 hours in one day (4 times) | 4 | i.p. | 281g | Same day | 28 | NA | Hyperactivity. | NA | |||||||||||
| Clemens 2007 [136] | Rat | Females | NA | 16 | Chronic | 1 injection per week for 16 weeks | 8 | i.p. | 238g | 7, 56, 112 days later | 28 | NA | Constant hyperactivity between weeks. | NA | |||||||||||
| Cohen 2005 [196] | Rat | Males | NA | 30 | Chronic | Twice a day (8 hours apart) | 20 | s.c. | 11-20 | 5 weeks, 1 day later | 21 | Neonatal: less total and central distance travelled, increased thigmotaxis. | NA | NA | |||||||||||
| Cohen 2005 [196] | Rat | Males | NA | 30 | Chronic | 4 times, at 2 intervals | 15 | s.c. | 82-100 | 5 weeks, 1 day later | 21 | Neonatal and adult: increased thigmotaxis. | NA | NA | |||||||||||
| Colussi-Mas 2008 [243] | Rat | Males | NA | 21 | Chronic | Once daily for 5 consecutive days | 10 | i.p. | “Adult” (250–300g) | Same ages | 21 | No effect. | NA | NA | |||||||||||
| Colussi-Mas 2008 [243] | Rat | Males | NA | 21 | Singular | NA | 5 | i.p. | “Adult” (250–300g) | Same ages | 21 | 5, 10 mg/kg: increased locomotion graph. 5 mg/kg: increased central time. | NA | NA | |||||||||||
| Colussi-Mas 2008 [243] | Rat | Males | NA | 21 | Chronic | Once daily for 5 consecutive days + this one after 2 days | 5 | i.p. | “Adult” (250–300g) | Same ages | 21 | Hyperlocomotion in, and time spent in, central zone | NA | NA | |||||||||||
| Cox 2014 [244] | Rat | Males | NA | 26 | Chronic | Daily for 4 days | 5, 10 | i.p. | 38-41 | 46 | NA | 10 mg/kg: decreased centre time. | NA | NA | |||||||||||
| Daza-Losada 2009 [221] | Mouse | Males | NA | 315 | Singular | NA | 5, 10, 20 | i.p. | 28 | 28 | 21 | 10, 20 mg/kg: increased hyperlocomotion. | NA | NA | |||||||||||
| Ebrahimian 2017 [245] | Mouse | Males | NA | 40 | Both | Single dose, twice | 20, 60 | p.o. | NA | 0 and 9 days later | 22-24 | 20 and 60 mg/kg: total distance travelled dose-dependently increased, rearing decreased. | NA | NA | |||||||||||
| Fantegrossi 2004 [246] | Mouse | Males | NA | 12 | Singular | NA | 32 | i.p. | 20-30g | Same age | 22 | Long-lasting hyperlocomotion (3 hours post-injection). | NA | NA | |||||||||||
| Ferraz-de-Paula 2011 [247] | Mouse | Males | NA | 14-16 | Singular | NA | 0.2-20 | i.p. | 60 | 67 | 22-26 | 5, 8, 10, 20 mg/kg: increased total distance travelled, peripheral time, locomotor activity; decreased frequency of rearing and grooming. 8, 10, 20 mg/kg: increased peripheral distance travelled. 1, 5, 20 mg/kg: increased central distance travelled. 1, 5, 10, 20 mg/kg: increased central time. 5, 10 mg/kg: increased distance travelled, mean locomotor activity; decreased number and time of head-dipping (hole-board). |
NA | NA | |||||||||||
| Study | Species | Sexes | Sexes Combined or Separated | Sample Size | Singular/Chronic Dosing | Chronic Timing | Dose (mg/kg) | Route | Treatment Age (PD) | Testing Age (PD) | Temperature (°C) | Males | Females | Both | |||||||||||
| Fone 2002 [131] | Rat | Males | NA | 36 | Chronic | Twice daily | 7.5 | i.p. | 39-41 | 39 | 21 | 7.5 mg/kg: sustained hyperlocomotion. Serotonin syndrome: extensive reciprocal forepaw treading, lateral head weaving, flat body posture. | NA | NA | |||||||||||
| García-Pardo 2017 [94] | Mouse | Males | NA | 14-16 | Singular | NA | 5, 10 | i.p. | 42 | 70, 71 | 35-37 | More centre entries. | NA | NA | |||||||||||
| Gold 1988 [248] | Rat | Males | NA | 60 | Singular | NA | 1.25, 2.5, 5, 10 | s.c. | “Adult” (250-400g) | Same day | NA | Hyperlocomotion in first 10 mins. 2.5-10 mg/kg: hypolocomotion for rest of 2 hours. Initially decreased, then increased, holepokes. Dose-dependent sustained decreased repeated:varied holepokes. Decreased, then increased, rearings. Dose-dependent centre avoidance, hyperlocomotion. 10 mg/kg: increased rearings in 2nd hour. 10 mg/kg: hyperlocomotion. | NA | NA | |||||||||||
| Gold 1988 [249] | Rat | Males | NA | 60 | Singular | NA | 0.63, 0.94 | s.c. | “Adult” (250-400g) | Same day | NA | More perseverative locomotion patterns. 0.63 mg/kg: decreased repeated:varied nosepokes. 0.94 mg/kg: decreased rearing. | NA | NA | |||||||||||
| Gold 1988 [249] | Rat | Males | NA | 60 | Singular | NA | 10 | s.c. | “Adult” (250-400g) | Same day | NA | Hyperlocomotion. | NA | NA | |||||||||||
| Gurtman 2002 [134] | Rat | Males | NA | 26 | Chronic | Each of 4 hours | 5 | i.p. | 90 | 118 | 22 | Hyperlocomotion. | NA | NA | |||||||||||
| Hegadoren 1995 [250] | Rat | Males | NA | 24 | Singular | NA | NA | i.p. | 250-400g | Same day | NA | 1st 30 mins.: rapid locomotor increase. Decreased yawning, mouth movements, lying down, stretching. Increased body adjustments, clockwise rotations. Complete insomnia. | NA | NA | |||||||||||
| Hiramatsu 1989 [251] | Rat | Males | NA | 21-27 | Singular | NA | 5, 10, 20 | s.c. | 200-300g | Same ages | 23 | Stereotyped sniffing, head-weaving, backpedalling, turning. NB: S(+) MDMA: more head-weaving, backpedalling, turning than R(-). | NA | NA | |||||||||||
| Ho 2004 [252] | Rat | Males | NA | 65 | Singular | NA | 7.5, 15 | i.p. | 271g | 9-10 days later | 22-24 | No effect. | NA | NA | |||||||||||
| Kalivas 1998 [253] | Rat | Males | NA | 24 | Chronic | 5 days: 5 mg/kg once daily, or 20 mg/kg twice daily | 5, 20 | s.c. | NA | NA | NA | Acute, 5 mg/kg, Day 2: increased horizontal activity, distance travelled, stereotypy. Chronic 5, 20 mg/kg for 4 days: increased activity. Day 19: more increase in horizontal activity, distance travelled, response greater. 2 days washout, daily 5 mg/kg: more horizontal activity, distance travelled. More activity at 30-90 mins. post-injection. | NA | NA | |||||||||||
| Study | Species | Sexes | Sexes Combined or Separated | Sample Size |
Singular/Chronic
Dosing |
Chronic Timing | Dose (mg/kg) | Route | Treatment Age (PD) | Testing Age (PD) | Temperature (°C) | Males | Females | Both | |||||||||||
| Kindlundh-Högberg 2009 [254] | Mouse | Males | NA | 12 | Chronic | 3 injections every 7th day for 4 days | 5 | i.p. | 120-180 | Same ages | 20 | Increased horizontal activity. 1st week: increased locomotor:horizontal ratio. | NA | NA | |||||||||||
| Kurling 2008 [225] | Rat | Males | NA | 12 | Singular | NA | 5 | i.p. | “Adult” (300-380g) | Same day | 21 | Increased locomotion, burst of rearings, slight agitation, stereotypies (intensive sniffing, head/body weaving, head-bobbing). |
NA | NA | |||||||||||
| Lebsanft 2005 [255] | Rat | Males | NA | 20 | Singular | NA | 5 | s.c. | 47-56 | Same day | 22.5 | No effect. | NA | NA | |||||||||||
| Llorente-Berzal 2013 [199] | Rat | Both | Separated | 60 | Chronic | Every 5 days, twice daily (4 hours apart) | 10 | s.c. | 30-45 | 71 | 22 | Increased thigmotaxis. | Increased thigmotaxis. | NA | |||||||||||
| Lorens 1990 [256] | Rat | Males | NA | 36-48 | Chronic | Every 12 hours for 4 consecutive days | 10, 20, 40 | s.c. | 225-250g | 2-3 weeks later | NA | No effect. | NA | NA | |||||||||||
| Ludwig 2008 [200] | Rat | Males | NA | 39+ | Singular | Single injection | 5 | s.c. | “Adult” (242-275g) | “Adult” (242-275g) | 26 | 5-10 mins.: increased total locomotion. 10-20 mins.: decreased rearing | NA | NA | |||||||||||
| Ludwig 2008 [200] | Rat | Males | NA | 39+ | Chronic | 5 daily injections | 5 | s.c. | “Adult” (242-275g) | “Adult” (242-275g) | 26 | After 10 mins.: increased locomotion. Multiple MDMA injections: increased central and total locomotion, decreased peripheral locomotion. | NA | NA | |||||||||||
| Ludwig 2008 [200] | Rat | Males | NA | 39+ | Both | Chronic, then single | 5 | s.c. | “Adult” (242-275g) | “Adult” (242-275g) | 26 | 1st 10 mins., multiple MDMA injections: decreased rearing. Multiple MDMA injections: increased central and total locomotion, decreased peripheral locomotion. Multiple doses: increased rearing. Check - Low doses had higher locomotor activity than high doses. - check. | NA | NA | |||||||||||
| McNamara 1995 [257] | Rat | Males | NA | 24 | Chronic | Twice daily for 4 days | 5, 10, 20 | i.p. | 200-250g | 7 days later | 22-24 | 10 and 20 mg/kg increased locomotor activity (experimental day 1, 2, 4). 20 mg/kg: increased locomotion (experimental day 3). | NA | NA | |||||||||||
| Mechan 2002 [258] | Rat | Males | NA | 16 | Singular | NA | 12.5 | i.p. | “Adult” (160-200g) | 9–11, 30–32, 71–73 days post-injection | 21 | White light: no effect. Red light: hyperlocomotion till significant on PD 73. | NA | NA | |||||||||||
| Miczek 1994 [227] | Mouse | Males | NA | 29 | Singular | NA | 0.3-10 | NA | “Adult” | Same day | 21 | 10 mg/kg: decreased rearing. | NA | NA | |||||||||||
| Morley 2000 [228] | Rat | Males | NA | 48 | Singular | NA | 1.25, 2.5, 5 | i.p. | 85-95 | 99-109 | 22 | Decreased centre time, increased defaecation. 5 mg/kg: hyperlocomotion. | NA | NA | |||||||||||
| Study | Species | Sexes | Sexes Combined or Separated | Sample Size | Singular/Chronic Dosing | Chronic Timing | Dose (mg/kg) | Route | Treatment Age (PD) | Testing Age (PD) | Temperature (°C) | Males | Females | Both | |||||||||||
| Morley 2001 [91] | Rat | Males | NA | 48 | Chronic | Each of 4 hours over 2 days | 5 | i.p. | 75-95 | 160-180 | 28 | Hyperlocomotion. | NA | NA | |||||||||||
| O'Loinsigh 2001 [259] | Rat | Males | NA | 12-14 | Chronic | Twice daily for 4 consecutive days | 20 | i.p. | 200-300g | 200-300g | 20-22 | Increased locomotion and stereotypy, decreased rearing | NA | NA | |||||||||||
| Olsen 2016 [260] | Rat | Males | NA | NA | Chronic | Twice | 0.75, 1.5, 3 | i.p. | 105 | 105 | NA | 1.5, 3 mg/kg: dose-dependently decreased response rate for repeated, as opposed to varied, tasks | NA | NA | |||||||||||
| Palenicek 2005 [261] | Rat | Both | Separated | 79 | Singular | NA | 2.5, 5, 10 | s.c. | 50 | 50 | 22-24 | Dose-dependently increased locomotion | Dose-dependently increased locomotion. 2.5 and 5 mg/kg: longer trajectory than males, increased thigmotaxis. | NA | |||||||||||
| Paleníček 2007 [262] | Rat | Both | NA | 88 | Singular | NA | 2.5, 5, 10 | s.c. | 150-220g | 150-220g | 22-24 | Females, 5 mg/kg: sniffing stereotypy. 10 mg/kg: sniffing stereotypy (only males in 2nd session). 2.5, 10 mg/kg in 1st session; 10 mg/kg in 2nd session: males > females. Females, 10 mg/kg: decreased stereotypy | |||||||||||||
| Paulus 1992 [263] | Rat | Males | NA | 47 | Singular | NA | MDMA: 1.25, 2.5, 5, 10 | s.c. | 250-300g | 250-300g | NA | Increased ratio of short:long microevent durations. 5, 10 mg/kg: straighter paths travelled | NA | NA | |||||||||||
| Paulus 1992 [263] | Rat | Males | NA | 61 | Singular | NA | (+)MDMA: 0.3, 1, 3, 10 | s.c. | 250-300g | 250-300g | NA | 3, 10 mg/kg: increased thigmotaxis. 10 mg/kg: straighter paths travelled. Hyperlocomotion | NA | NA | |||||||||||
| Paulus 1992 [263] | Rat | Males | NA | 62 | Singular | NA | (-)MDMA: 1, 3, 10, 30 | s.c. | 250-300g | 250-300g | NA | Long straight paths with thigmotaxis. 10, 30 mg/kg: straighter paths. 30 mg/kg: hyperactivity | NA | NA | |||||||||||
| Piper 2004 [203] | Rat | Males | NA | 16 | Chronic | On every 5th day on PD 35-60, twice daily, 4 hours apart each | 10 | s.c. | 35-60 | 65 | 22 | No effect. | NA | NA | |||||||||||
| Piper 2005 [204] | Rat | Males | NA | 20 | Chronic | Hourly intervals over 4 hours, once every 5 days | 5 | s.c. | 35-70 | 35, 45, 60, 65 | 22 | PD 35: increased headweaving. Hyperlocomotion at 2-4 mins., hypolocomotion at 7-10 mins. |
NA | NA | |||||||||||
| Piper 2008 [205] | Rat | Males | NA | 20-24 | Chronic | 4 doses, 1 each hour | 10 | s.c. | “Young adult” (307.7g) | Young adult | 23 | Hole-board: fewer hole entries after MDMA on 2nd injection. |
NA | NA | |||||||||||
| Study | Species | Sexes | Sexes Combined or Separated | Sample Size | Singular/Chronic Dosing | Chronic Timing | Dose (mg/kg) | Route | Treatment Age (PD) | Testing Age (PD) | Temperature (°C) | Males | Females | Both | |||||||||||
| Powell 2004 [264] | Mouse | Both | Combined | 15-33 | Singular | NA | 10, 20, 30 | i.p. | 150 | 150 | NA | NA | NA | Hyperlocomotion, straight perseverative movements | |||||||||||
| Procopio-Souza 2011 [85] | Mouse | Males | NA | 19 | Singular | NA | 10 | i.p. | 90 | Same day | 22-23 | Increased bouts of locomotion. | NA | NA | |||||||||||
| Procopio-Souza 2011 [85] | Mouse | Males | NA | 19 | Singular | NA | +10 | i.p. | 97 | Same day | 22-23 | More bouts of hyperlocomotion with MDMA pretreatment. | NA | NA | |||||||||||
| Quinteros-Munoz 2010 [265] | Rat | Males | NA | 56-77 | Singular | NA | 0.25, 0.5, 1, 3, 5, 10 | i.p. | 200-230g | 200-230g | NA | 1 mg/kg: increased grooming; declined after higher doses. 10 mg/kg: decreased head shakes | NA | NA | |||||||||||
| Shen 2011 [233] | Rat | Males | NA | 60 | Chronic | 2, every 5th day | 10 | s.c. | 50-60 | 70 | 26 | No effect. | NA | NA | |||||||||||
| Shen 2011 [233] | Rat | Males | NA | 19 | Chronic | 2, every 5th day | 10 | s.c. | 50-60 | 74 | 26 | Holeboard: decreased varied entries. | NA | NA | |||||||||||
| Shen 2011 [233] | Rat | Males | NA | 19 | Chronic | 2, every 5th day | 10 | s.c. | 48-58 | 68 | 26 | No effect. | NA | NA | |||||||||||
| Slamberova 2018 [266] | Mouse | Males | NA | 16 | Singular | NA | 5 | s.c. | 77-97 | 77-97 | 22-24 | Increased locomotion, distance travelled, average speed. No effect on grooming duration. | NA | NA | |||||||||||
| Stanley 2007 [267] | Rat | Males | NA | 8 | Singular | NA | 10 | i.p. | 250-300g | 250-300g | 22 | Stereotypic-included behaviour increased. | NA | NA | |||||||||||
| Thompson 2009 [82] | Rat | Males | NA | 36 | Singular | NA | 5 | i.p. | “Adult” (345g) | Same day | 28 | Hyperlocomotion, more central time. | NA | NA | |||||||||||
| Walker 2010 [268] | Rat | Males | NA | 30-34 | Singular | NA | 5 | i.p. | 28, 42, 65 | 28, 42, 65 | NA | Early hyperlocomotion (PD 28 < 42, 65). No stereotypy effects. | NA | NA | |||||||||||
| Yamamotová 2012 [269] | Rat | Males | NA | 20 | Singular | NA | 5 | s.c. | 85-90 | 85-90 | NA | Increased stereotypy. | NA | NA | |||||||||||
| Yang 2011 [270] | Rat | Females | NA | 26 | Singular | NA | 5 | i.p. | “Adult” (180-190g) | “Adult” (180-190g) | 21 | NA | Increased horizontal activity and total distance travelled (experimental day 2 > day 1). |
NA | |||||||||||
| Study | Species | Sexes | Sexes Combined or Separated | Sample Size | Singular/Chronic Dosing | Chronic Timing | Dose (mg/kg) | Route | Treatment Age (PD) | Testing Age (PD) | Temperature (°C) | Males | Females | Both | |||||||||||
| - | - | - | - | - | - | - | - | - | - | - | - | - | Decreased vertical activity (experimental day 2 > day 1). 5 mg/kg: increased total distance travelled, horizontal activity, stereotypies; decreased vertical acitivity (10-110 mins. post injection). | ||||||||||||
| Yang 2011 [270] | Rat | Females | NA | 26 | Singular | 6 consecutive days | 5 | i.p. | 85-87 | 85-87 | 21 | NA | Increased stereotypies, decreased vertical activity (0-20 mins. post-injection). Increased horizontal activity (30 mins.-2 hours post-injection). 5 mg/kg: increased total distance travelled, horizontal activity, stereotypies; decreased vertical acitivity (10-110 mins. post injection). Chronic dosing had no effect. 5 mg/kg: increased/decreased locomotion (experimental day 11 > day 2). | NA | |||||||||||
| Study | Species | Sexes |
Sexes
Combined or Separated |
Sample Size |
Singular/
Chronic Dosing |
Chronic Timing | Dose (mg/kg) | Route | Treatment Age (PD) | Testing Age (PD) | Temperature (°C) | Males | Females | Both | |||||||||||
| Young 2008 [271] | Mouse | Males | NA | 48 | Singular | NA | (±)-MDMA: 0.3, 1, 3, 10, 30 | i.p. | 27-34g | 27-34g | 22 | Hyperlocomotion. 30 mg/kg: decreased thiogmotaxis. | NA | NA | |||||||||||
| Young 2008 [271] | Mouse | Males | NA | 48 | Singular | NA | S(+)-MDMA: 0.3, 1, 3, 10, 30 | 27-34g | 27-34g | 22 | Hyperlocomotion. | NA | NA | ||||||||||||
| Young 2008 [271] | Mouse | Males | NA | 64 | Singular | NA | R(-)-MDMA: 0.3, 1, 3, 10, 17, 30, 50 | 27-34g | 27-34g | 22 | Hyperlocomotion. | NA | NA | ||||||||||||