Use of osmotic minipumps for sustained drug delivery in rat pups: effects on physical and neurobehavioural development

Abstract

Osmotic minipumps are often used as an alternative to repetitive injections for prolonged drug delivery in adult rats. The appropriateness of using this technology for sustained drug delivery in newborn rats, however, has not been validated. Our objective was to determine if implantation of osmotic minipumps, and the associated surgical stress, during a critical developmental period, affects early development and subsequent behaviour. SD rat pups were assigned to control, minipump, or sham surgery treatment conditions ( n=12/group). On P8, pups were briefly anaesthetised with isoflurane in oxygen, and Alzet 1007D osmotic minipumps, loaded with normal saline, were aseptically implanted (removed on P17). Sham-treated rats received identical treatment (with the exception of pump placement), while control pups were left undisturbed. Development was examined daily using a standard test battery (P9–P21), and learning and memory in pups was assessed in a T-maze (P15, P17 and P19). Weight (P27 and P72), open-field (P25, P26 and P27) and novel water maze performance (P60–P72) were examined in the resulting adult. With the exception of a transient decrease in weight gain, pump-treated animals did not differ from either sham or control rats, on any pre- or postweaning assessment. Based on these results we conclude that the use of osmotic minipumps in rat pups is a viable alternative to repeated injections for sustained drug delivery.