Abstract
With few exceptions, the preclinical evaluation of drugs is undertaken in healthy, young adult animals. The available literature on the interaction between the age of animals and drug effects are largely concerned with the age span from neonate to young adult, i.e., developmental studies. Kato and Takanaka (1) have demonstrated depressed in vitro drug metabolism of several drugs including hexobarbital and me-probamate in 250-600 day old rats as compared to 100 day old rats. These investigators (2) also found an increased duration of action and a decreased rate of decline of plasma pentobarbital levels with increasing age. Ziem et al. (3) have reported increased central nervous system sensitivity to amphetamine in 12-14 mo old rats when compared with 3 mo old animals.
The work presented here was performed to demonstrate age-related alterations in the responsiveness of mature rats to centrally acting drugs and to emphasize the importance of regarding the age of the animal as a significant factor in assessing drug response. Responses to sodium hexobarbital, chlorpromazine HCl, morphine SO4 and d-amphetamine SO4 were evaluated in 2.5-3 mo old and 9-10 mo old male rats.
Methods. Male, albino Cox/Sprague-Dawley rats were obtained from Laboratory Supply Co., Indianapolis and housed in community cages for 1-2 weeks prior to use. Wayne Lab Bloks and tap water were supplied ad libitum. Room lights were cycled from 6 am to 8 pm daily and temperature was kept constant at 25 ± 1.0°.
The electroencephalogram was recorded from three cortical electrodes (SS fillister head machine screws 0-80 × 1/8 in.) implanted 2 mm to either side of the saggital suture and 2 mm posterior to the bregma. A third screw was placed 1 cm anterior to the bregma and 1 mm to the right of the saggital suture.
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