Causal and functional interpretation of mu- and delta-opioid receptor profiles in mesoaccumbens and nigrostriatal pathways of an oral stereotypy phenotype

Abstract

Spontaneous stereotypic behaviours are repetitive, compulsive, topographically invariant response patterns commonly observed in captive or domestic animals, which have been linked to dysfunction of basal ganglia input/output pathways. There is evidence that endogenous opioids play a key regulatory role in basal ganglia direct and indirect pathways, but their precise role, both causally and functionally, in spontaneous stereotypic behaviour is unclear. Here we examined the profile of mu- and delta-opioid receptors (density [Bmax] and affinity [Kd]) of basal ganglia structures in stereotypy (n = 10) and non-stereotypy (n = 10) animals using a competitive ligand binding approach. Mu receptor densities were significantly higher in the nucleus accumbens (p < 0.001), ventral tegmentum area (p < 0.001) and caudate nuclei (p < 0.001) of stereotypy compared to control animals. No differences were observed for delta Bmax values in any of the brain regions studied (p > 0.15). Receptor binding affinity was only found to be significantly different between control and stereotypy animals for mu receptors on the caudate region; (p < 0.001). Our findings suggest that increased inhibition (via mu-opioid receptors) of the indirect (dorsal striatopallidal) pathways are associated with spontaneous stereotypy development. Data also suggested that different types of spontaneous stereotypies (e.g. oral versus locomotor) within or a cross species may have a different neurological basis. This may have important implications for understanding the aetiology and function of these behaviours. In some instances (oral stereotypy), the behaviour may be associated with allostasis, a process that could enhance the reward value of appetitive behaviour performance (as a starting point of stereotypy development).