Nifedipine suppresses self-injurious behaviors in animals

Abstract

Self-injurious behavior is a common problem in many developmental disorders. The neurobiology of this behavior is not well understood, but the differing behavioral manifestations and associations with different disorders suggest that the underlying biological mechanisms are heterogeneous. The behavioral and biological heterogeneity is also evident in several animal models, where different manifestations can be provoked under different experimental conditions. Identifying commonalities among the different mechanisms is likely to be helpful in the design of treatments useful for the broadest populations of patients. The current studies reveal that nifedipine suppresses self-injurious behavior in 4 unrelated animal models: acute administration of high doses of +/-BayK 8644 or methamphetamine in mice, dopamine agonist treatment in rats with lesions of dopamine pathways during early development and repeated administration of pemoline in rats. The effect of nifedipine does not appear to be due to nonspecific mechanisms, such as sedation, since other classes of behaviors are unaffected or exaggerated. These results suggest that nifedipine may target a common biological mechanism in the expression of self-injurious behavior, and they suggest it should be considered in the treatment of self-injury in humans.

Fig. 1

Calcium channel antagonists suppress SB and SIB in response to ±BayK 8644. The top row of panels shows the frequencies of SB, while the bottom row shows SIB. The calcium channel antagonists (20 mg/kg each) are noted above the panels. The results for these antagonists are shown as black bars, while the corresponding control group is shown in gray. Ten mice were tested under each drug and dose condition. The results of the χ² statistical analysis comparing the influence of the antagonist with its corresponding control group are shown within each panel.

Fig. 2

Nifedipine alters the frequency of stereotypical behaviors after a single dose of methamphetamine. The results show the average percentage of the lime the animals spent engaging in the behavior, expressed as a percentage of vehicle-treated controls (±SEM). With 10 mg/kg of nifedipine, SB and taffy pulling were significantly decreased, while repetitive sniffing or licking/biting the cage walls were increased (p < 0.01).

Fig. 3

Nifedipine (10 mg/kg) alters the frequency of stereotypical behaviors after apomorphine treatment of rats with neonatal 60HDA lesions. The fraction of lime that nifedipinc-prctrcatcd raLs were observed engaging in behaviors is expressed as the average percent of vehicle-treated rats (±SEM). Compared to vehicle, pretreatment with 10 mg/kg of nifedipine significantly reduced the percentage of time the rats spent taffy pulling (p < 0.001) and significantly increased the time they spent sniffing (p<0.0l). The trends towards increased gnawing/licking the cage and reduced SB were not significant (p > 0.10).

Fig. 4

Nifedipine reduces SB and SIB in pemoline-treated rats. a Average duration of self-injurious oral contact, measured as percentage of the time during which sustained oral contact occurred during the videotaped overnight time samples, b Tissue injury scores, as measured according to table 1. All values are expressed as group means ± SEM. Significant differences between rals treated with vehicle or nifedipine (LSD) are depicted as follows: ^a p <; 0.05 for comparisons between nifedipine at 30 mg/kg and vehicle, ^b p < 0.05 for comparisons between nifedipine at 10 mg/kg and vehicle, and ^c p < 0.05 for comparisons between nifedipine at 3 mg/kg and vehicle.

Fig. 5

The effect of nifedipine on other pemoline-induced behaviors in rats. The time spent grooming (a; F_4,72 = 4.6, p < 0.01) or inactive (b; F_{4, 72} = 6.7, p < 0.01) and the amount of locomotion (c; F_{4, 72} = 23.9, p < 0.01) recorded on videotapes overnight all decreased significantly across the days of ilie experiment, but no significant between-group effects or group by time interaction effects were found.