The effects of 8-OH-DPAT and (+/-)-pindolol on isolation-induced ultrasonic vocalizations in 3-, 10-, and 14-day-old rats.

It has been established that administration of 5-HT1A agonists attenuates the rate of isolation-induced ultrasonic vocalizations (USV) in 10-day-old rat pups. In this study we extended these findings by examining the effects of administration of the serotonergic 1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and mixed 5-HT1A antagonist/beta adrenergic antagonist, (+/-)-pindolol, in 3-, 10-, and 14-day-old rat pups in order to assess the effect of these drugs from a developmental perspective. At all three ages, 8-OH-DPAT significantly reduced the rate of isolation-induced USV. While only the highest dose (1.0 mg/kg) of 8-OH-DPAT administered to the 10- and 14-day-olds significantly reduced the rate of vocalization, both the 0.1- and 1.0-mg/kg doses significantly attenuated the vocalization rate in the 3-day-olds. Pindolol administration did not alter the rate of USV at any age nor did it block the quieting effect that generally occurs when an anesthetized littermate is placed with the isolated pup. We conclude that 8-OH-DPAT is effective as early as 3 days of age in the quieting of isolation-induced USV and that the regional age-dependent development of 5-HT1A receptors and projections are important factors in the observed differential sensitivity to 8-OH-DPAT administration during development.