Table 4.
Behavioural alterations in the VPA rat model of autism.
Function | Task | Effect | Species | Gender | Dose (mg/kg) | GD VPA admin | PND testing | Reference |
---|---|---|---|---|---|---|---|---|
Motor development, locomotion, vestibular function (focal prenatal VPA exposure) | ||||||||
Vestibular function, motor development, | Negative geotaxis | No effect | Rat | M | 600 | 12.5 | 7–10 | Schneider and Przewlocki, 2005 |
Vestibular function, motor development, | Negative geotaxis | No effect | Mouse | M, F | 600 | 13 | 13–19 | Wagner et al., 2006 |
Motor development | Surface righting | Impaired | Mouse | M, F | 600 | 13 | 5–9 | Wagner et al., 2006 |
Motor development | Mid-air righting | Impaired | Mouse | M, F | 600 | 13 | 13–19 | Wagner et al., 2006 |
Motor development | Hanging wire grip strength | Enhanced | Mouse | M, F | 200 | 13 | 13–19 | Wagner et al., 2006 |
Motor development | Balance beam | No effect | Mouse | M, F | 600 | 13 | 20–26 | Wagner et al., 2006 |
Motor development | Swim performance | Impaired | Rat | M | 600 | 12.5 | 8, 12 | Schneider and Przewlocki, 2005 |
Motor development | Swim performance | No effect | Rat | M | 600 | 12.5 | 10, 16 | Schneider and Przewlocki, 2005 |
Locomotion | Open field | Enhanced | Rat | 800 | 9 | 18 | Tsujino et al., 2007 | |
Locomotion | Opto-Varimex cage | Enhanced | Rat | M | 600 | 12.5 | 30–50 | Schneider and Przewlocki, 2005 |
Locomotion | Opto-Varimex cage | Enhanced | Rat | M | 600 | 12.5 | 90–120 | Schneider and Przewlocki, 2005 |
Locomotion | Plexi-glass box | Enhanced | Mouse | M, F | 600 | 13 | 20–26 | Wagner et al., 2006 |
Locomotion | EPM | No effect | Rat | M, F | 500 | 12.5 | 110–120 | Markram et al., 2007 |
Motor development, locomotion, vestibular function (prolonged prenatal VPA exposure) | ||||||||
Vestibular function, motor development | Negative geotaxis | Impaired | Mouse | M, F | 200 | 12–17 | 13–19 | Wagner et al., 2006 |
Motor development | Surface righting | No effect | Mouse | M, F | 200 | 12–17 | 5–9 | Wagner et al., 2006 |
Motor development | Mid-air righting | No effect | Mouse | M, F | 200 | 12–17 | 13–19 | Wagner et al., 2006 |
Motor development | Hanging wire grip strength | No effect | Mouse | M, F | 200 | 12–17 | 13–19 | Wagner et al., 2006 |
Motor development | Balance beam | No effect | Mouse | M, F | 200 | 12–17 | 20–26 | Wagner et al., 2006 |
Motor development | Swim performance | No effect | Rat | M, F | 150 | 7–18 | 50 | Vorhees, 1987 |
Motor development | Swim performance | Impaired | Rat | M, F | 200 | 7–18 | 50 | Vorhees, 1987 |
Locomotion | Activity meter | No effect | Rat | M, F | 150 | 7–18 | 7,9, 11 | Vorhees, 1987 |
Locomotion | Activity meter | No effect | Rat | M, F | 200 | 7–18 | 7,9, 11 | Vorhees, 1987 |
Locomotion | Open field | No effect | Rat | M, F | 150 | 7–18 | 40–42 | Vorhees, 1987 |
Locomotion | Open field | No effect | Rat | M, F | 200 | 7–18 | 40–42 | Vorhees, 1987 |
Locomotion | Plexi-glass box | No effect | M | M, F | 200 | 12–17 | 20–26 | Wagner et al., 2006 |
Exploration (focal prenatal VPA exposure) | ||||||||
Exploration | Hole board | Reduced | Rat | M | 600 | 12.5 | 30–50 | Schneider and Przewlocki, 2005 |
Exploration | Hole board | Reduced | Rat | M | 600 | 12.5 | 90–120 | Schneider and Przewlocki, 2005 |
Exploration (prolonged prenatal VPA exposure) | ||||||||
Activity, Eploration | Figure 8 | No effect | Rat | M, F | 150 | 7–18 | 40–42 | Vorhees, 1987 |
Activity, Eploration | Figure 8 | No effect | Rat | M, F | 200 | 7–18 | 40–42 | Vorhees, 1987 |
Eploration | Hole board | Enhanced | Rat | M, F | 150 | 7–18 | 45 | Vorhees, 1987 |
Eploration | Hole board | Reduced | Rat | M, F | 200 | 7–18 | 45 | Vorhees, 1987 |
Circadian Rhythm | ||||||||
Locomotion under 12 hours light/dark cycle | Plastic cages | Enhanced in light phase | Rat | 800 | 9 | 28–43 | Tsujino et al., 2007 | |
Feeding under 12 hours light/dark cycle | Plastic cages | Impaired cycle variation | Rat | 800 | 9 | 28–43 | Tsujino et al., 2007 | |
Perception (focal prenatal VPA exposure) | ||||||||
Olfactory | Olfactory discrimination, nest seeking | Impaired | Rat | M | 600 | 12.5 | 9 | Schneider et al., 2001 |
Olfactory | Olfactory discrimination, nest seeking | No effect | Rat | M | 600 | 12.5 | 10, 11 | Schneider and Przewlocki, 2005 |
Tactile | Von Frey test | Enhanced | Rat | M | 600 | 12.5 | 30–50 | Schneider and Przewlocki, 2005 |
Tactile | Von Frey test | No effect | Rat | M | 600 | 12.5 | 90–120 | Schneider and Przewlocki, 2005 |
Auditory | Auditory startle | No effect | Rat | M | 600 | 12.5 | 30–50 | Schneider and Przewlocki, 2005 |
Auditory | Auditory startle | No effect | Rat | M | 600 | 12.5 | 90–120 | Schneider and Przewlocki, 2005 |
Auditory | Auditory startle | No effect | Rat | M, F | 500 | 12.5 | 80–90 | Markram et al., 2007 |
Sensori-motor gating | PPI | Reduced | Rat | M | 600 | 12.5 | 30–50 | Schneider and Przewlocki, 2005 |
Sensori-motor gating | PPI | Reduced | Rat | M | 600 | 12.5 | 90–120 | Schneider and Przewlocki, 2005 |
Sensori-motor gating | PPI | Reduced | Rat | M, F | 500 | 12.5 | 80–90 | Markram et al., 2007 |
Perception (prolonged prenatal VPA exposure) | ||||||||
Auditory | Auditory startle | No effect | Rat | M, F | 150 | 7–18 | 85 | Vorhees, 1987 |
Auditory | Auditory startle | Reduced | Rat | M, F | 200 | 7–18 | 85 | Vorhees, 1987 |
Tactile | Air-puff startle | No effect | Rat | M, F | 150 | 7–18 | 85 | Vorhees, 1987 |
Tactile | Air-puff startle | Reduced | Rat | M, F | 200 | 7–18 | 85 | Vorhees, 1987 |
Nociception (focal prenatal VPA exposure) | ||||||||
Tactile | Tail flick | Reduced | Rat | M | 600 | 12.5 | <30 | Schneider et al., 2001 |
Tactile | Tail flick | Reduced | Rat | M | 600 | 12.5 | 30–50 | Schneider and Przewlocki, 2005 |
Tactile | Tail flick | Reduced | Rat | M | 600 | 12.5 | 90–120 | Schneider and Przewlocki, 2005 |
Tactile | Tail flick | Reduced | Rat | M | 600 | 12.5 | >90 | Schneider et al., 2001 |
Thermal | Hot plate | No effect | Rat | M | 600 | 12.5 | <30 | Schneider et al., 2001 |
Thermal | Hot plate | Reduced | Rat | M | 600 | 12.5 | 30–50 | Schneider and Przewlocki, 2005 |
Thermal | Hot plate | Reduced | Rat | M | 600 | 12.5 | 90–120 | Schneider and Przewlocki, 2005 |
Thermal | Hot plate | Reduced | Rat | M | 600 | 12.5 | >90 | Schneider et al., 2001 |
Thermal | Hot plate | Reduced | Rat | M, F | 500 | 12.5 | 80–90 | Markram et al., 2007 |
Anxiety (focal prenatal VPA exposure) | ||||||||
Anxiety | EPM | Enhanced | Rat | M | 600 | 12.5 | 30–50 | Schneider et al., 2006 |
Anxiety | EPM | Enhanced | Rat | M | 600 | 12.5 | 60–90 | Schneider et al., 2007 |
Anxiety | EPM | Enhanced | Rat | M | 600 | 12.5 | 90–120 | Schneider et al., 2006 |
Anxiety | EPM | Enhanced | Rat | M, F | 500 | 12.5 | 110–120 | Markram et al., 2007 |
Anxiety (prolonged prenatal VPA exposure) | ||||||||
Anxiety | Open field | No effect | Rat | M, F | 150 | 7–18 | 40–42 | Vorhees, 1987 |
Anxiety | Open field | Enhanced | Rat | M, F | 200 | 7–18 | 40–42 | Vorhees, 1987 |
Social behaviours (focal prenatal VPA exposure) | ||||||||
Social behaviour | Free interaction | Impaired | Rat | M | 600 | 12.5 | 30–50 | Schneider and Przewlocki, 2005 |
Social behaviour | Free interaction | Impaired | Rat | M, F | 500 | 12.5 | 90–100 | Markram et al., 2007 |
Social behaviour | Free interaction | Impaired | Rat | M | 600 | 12.5 | 90–120 | Schneider and Przewlocki, 2005 |
Stereotyped, repetitive behaviours (focal prenatal VPA exposure) | ||||||||
Repetitive behaviour | Opto-Varimex cage | Enhanced | Rat | M | 600 | 12.5 | 30–50 | Schneider and Przewlocki, 2005 |
Repetitive behaviour | Opto-Varimex cage | Enhanced | Rat | M | 600 | 12.5 | 90–120 | Schneider and Przewlocki, 2005 |
Spontan. alterations | Y-maze | Reduced | Rat | M, F | 500 | 12.5 | 80–90 | Markram et al., 2007 |
Stereotyped, repetitive behaviours (prolonged prenatal VPA exposure) | ||||||||
Spontan. alterations | T-maze | No effect | Rat | M, F | 150 | 7–18 | 70 | Vorhees, 1987 |
Spontan. alterations | T-maze | Reduced | Rat | M, F | 200 | 7–18 | 70 | Vorhees, 1987 |
Learning and memory (focal prenatal VPA exposure) | ||||||||
Spatial learning | Morris water maze | Impaired | Mouse | M, F | 600 | 13 | 20–26 | Wagner et al., 2006 |
Spatial learning | Object recognition | No effect | Rat | M | 600 | 12.5 | 60–90 | Schneider et al., 2007 |
Spatial learning | Morris water maze | No effect | Rat | M, F | 500 | 12.5 | 90–110 | Markram et al., 2007 |
Eye blink conditioning | Discriminative eye-blink conditioning | Enhanced | Rat | M, F | 600 | 12 | 26–31 | Stanton et al., 2006 |
Fear conditioning | Auditory fear conditioning training | No effect | Rat | M, F | 500 | 12.5 | 120–122 | Markram et al., 2007 |
Fear conditioning | Auditory fear generalization | Enhanced | Rat | M, F | 500 | 12.5 | 124 | Markram et al., 2007 |
Fear conditioning | Auditory fear memory | Enhanced | Rat | M, F | 500 | 12.5 | 124–174 | Markram et al., 2007 |
Fear conditioning | Contextual fear memory | Enhanced | Rat | M, F | 500 | 12.5 | 123–173 | Markram et al., 2007 |
Conditioned place aversion | Conditioned place aversion to naloxone | Impaired | Rat | M | 600 | 12.5 | 60–90 | Schneider et al., 2007 |
Fear extinction | Contextual fear extinction | Impaired | Rat | M, F | 500 | 12.5 | 174–180 | Markram et al., 2007 |
Fear extinction | Tone fear extinction in same context | Impaired | Rat | M, F | 500 | 12.5 | 174–180 | Markram et al., 2007 |
Fear extinction | Tone fear extinction in different context | No effect | Rat | M, F | 500 | 12.5 | 174–180 | Markram et al., 2007 |
Reversal learning | Discriminative eye-blink reversal | Impaired | Rat | M, F | 600 | 12 | 26–31 | Stanton et al., 2006 |
Learning and memory (prolonged prenatal VPA exposure) | ||||||||
Spatial learning | Cincinnati water maze | No effect | Rat | M, F | 150 | 7–18 | 51–54; 57–58 | Vorhees, 1987 |
Spatial learning | Cincinnati water maze | No effect | Rat | M, F | 200 | 7–18 | 51–54; 57–58 | Vorhees, 1987 |
Spatial learning | Morris water maze | No effect | Mouse | M, F | 200 | 12–17 | 20–26 | Wagner et al., 2006 |
Spatial reversal learning | Cincinnati water maze | No effect | Rat | M, F | 150 | 7–18 | 59–61; 64–66 | Vorhees, 1987 |
Spatial reversal learning | Cincinnati water maze | M No effect F Impaired | Rat | M, F | 200 | 7–18 | 59–61; 64–66 | Vorhees, 1987 |
Results describe the VPA-treated offspring group relative to controls. Abbreviations: ED, embryonic day; EPM, elevated plus maze; F, female; M, male; N, number; PND, postnatal day; PPI, pre-pulse inhibition; VPA, valproic acid.