Species differences in behavioural effects of rolipram and other adenosine cyclic 3h, 5h-monophosphate phosphodiesterase inhibitors

Abstract

The effect of the phosphodiesterase (PDE) inhibitors rolipram, Ro 20-1724 and isobutylmethylxanthine (IBMX) on motor behaviour and rectal temperature was studied in mice, rats and guinea pigs following intraperitoneal administration (0.39 to 25 mg/kg). The selective adenosine cyclic 3′, 5′-monophosphate (cAMP) PDE inhibitors rolipram and Ro 20-1724 in each species caused a dissimilar pattern of neurotropic effects: Hypothermia andhypokinesia in mice, hypothermia,hypokinesia and head twitches in rats, hypothermia,hyperkinesia and head twitches in guinea pigs. The head twitches were associated with forepaw shaking and increased grooming. Rolipram was the most potent compound in the three species. In guinea pigs it was less active than in rats or mice. Ro 20-1724 was approx. 15 to 30 times less potent in inducing the characteristic alterations in the various species. The alkylxanthine PDE inhibitor IBMX, 0.39 to 6.25 mg/kg, slightly stimulated the locomotor activity of mice and rats, most probably due to antagonism of central adenosine actions. IBMX, 6.25 to 25 mg/kg, caused a pattern of neurotropic effects identical to that produced by the selective cAMP PDE inhibitors, indicating the prevalence of the cAMP PDE inhibitory action over the adenosine antagonistic action at higher dosages. IBMX was approx. as potent as Ro 20-1724 in this respect. The species differences in the neurotropic responses to cAMP PDE inhibitionin vivo presumably reflect similar differences in the extent of cAMP accumulation in brain tissue of the three speciesin vitro. Enhanced availability of brain cAMPin vivo in the various rodent species seems to be correlated with diverse patterns of more or less complex motor behavioural symptoms.