Sound pressure level and noradrenergic influences on audiogenic seizures in DBA mice

In Experiment 1,21-day-old DBA mice (N = 38) were exposed to different levels of sound intensity (100,110,120 dB SPL) in order to determine the relationship between sound intensity and audiogenic seizure (AGS) activity, and to find an intensity that could produce a baseline from which statistically significant increases (proconvulsant effects) and decreases (anticonvulsant effects) could be measured. The relationship between sound intensity (100,110,120,126 dB SPL) and AGS severity was also examined in 30-day-old mice (N = 40). At both ages, as sound intensity was increased, AGS activity increased; however, the higher intensities were less effective in eliciting the full AGS syndrome in the older mice. In Experiment 2, a test stimulus of 110 dB was used to evaluate the effects of methoxyamine (N = 46), prazocin (N = 46) and yohimbine (N = 71) on AGS at the age of peak susceptibility (21 days). These drugs act to increase seizure activity, or as alpha-1 antagonists and alpha-2 antagonists, respectively. Significant proconvulsant effects of methoxyamine (50,100,140 mg/kg) were expected and found. Also expected and found were significant anticonvulsant effects of prazocine (1,2,4,8 mg/kg), indicating that alpha-1 noradrenergic receptors may have proconvulsant activity in the AGS syndrome. The nonselective alpha-2 antagonist yohimbine (0.25, 0.50,1,2,4,8 mg/kg) only produced anticonvulsant effects at high doses (2,4,8 mg/kg). The results were discussed in terms of the midbrain adrenoceptor hypothesis of AGS.