Perinatal exposure to delta 9-tetrahydrocannabinol increases presynaptic dopamine D2 receptor sensitivity: a behavioral study in rats.

The endogenous cannabinoid system is a relevant modulator of dopaminergic synapses in dorsal striatum. Perinatal exposure to cannabinoid receptor agonists has been described to affect the development of dopaminergic circuits in rat brain. The epigenetic alterations described affected both dopamine neurons and dopamine receptor-expressing neurons. The present work has been designed to explore the effects of maternal exposure to orally delivered Delta(9)-tetrahydrocannabinol, (Delta(9)-THC 0.1, 0.5, 2 mg/kg) on the behavioural responses to the dopamine receptor agonists apomorphine (0.1 mg/kg) and quinpirole (0.5 mg/kg), at doses that target presynaptic dopamine D2 receptors. Maternal exposure to Delta(9)-THC affected both the developmental pattern of motor behaviours, and the behavioural responses to acute injections of apomorphine and quinpirole, tested in an open field. The effects were sex dimorphic, being more intense in male animals. Perinatal exposure to Delta(9)-THC resulted in enhanced presynaptic dopamine D2 receptor mediated responses such as immobility and inhibition of locomotion. Additionally, postsynaptic dopamine D2 receptor agonist-induced stereotypes were reduced in the group exposed to the highest dose of Delta(9)-THC (2 mg/kg). However, the late-onset pattern of behavioural activation observed after acute quinpirole exposure was equal in vehicle- and cannabinoid-treated animals. These effects suggest that perinatal exposure to Delta(9)-THC affects the functionality of dopaminergic autoreceptors, inducing a greater sensitivity to the presynaptic actions of dopamine D(2) receptor agonists.