A dose response study of effects of 8-OH-DPAT on locomotor sensitization to quinpirole

Abstract

Behavioural sensitization models are useful for understanding many disorders, including obsessive-compulsive disorder and drug addiction. Many of these models are produced by sensitization of dopamine neurotransmission, resulting in behaviours which include increased locomotor activity. Alterations to dopamine-mediated locomotor sensitization may be possible via activation of serotonergic neurotransmission, and there is evidence to suggest this may be through repeated activation of serotonin 1A receptors. The current study examines the development of locomotor sensitization in an animal model via repeated exposure of both a dopamine (D2R/D3R) and serotonin 1A (5-HT1A) agonist. To examine this, male Long-Evans rats were exposed to 10 injections of a combination of different doses of quinpirole and 8-OH-DPAT and tested in activity chambers for locomotor stimulation (measured by total distance travelled). Animals were then exposed to challenges of quinpirole, and 8-OH-DPAT and tested again for locomotor activity. Results showed that high doses of quinpirole or 8-OH-DPAT induced locomotor sensitization. However, when the two drugs were co-administered, 8-OH-DPAT displayed some initial disruption of quinpirole-induced sensitization. Animals sensitized to either quinpirole or 8-OH-DPAT did show higher locomotion when challenged with the drug to which they were sensitized. However, simultaneous quinpirole and 8-OH-DPAT sensitization seemed to prevent maximal responding when challenged with quinpirole. In all, our data suggests that sensitization to quinpirole and 8-OH-DPAT is occurring via separate neural mechanisms, with 5-HT1A agonism interfering with development of dopaminergic (D2R) sensitization.