Deafferentation elicits increased dopamine-sensitive adenylate cyclase and receptor binding in the olfactory tubercle

Abstract

Removal of a major non-catecholaminergic output from the olfactory bulb elicits sprouting of dopaminergic axons in the olfactory tubercle. The functional consequences of this increased dopaminergic innervation are presently not known. This study examined the question of whether lesion- induced sprouting of dopaminergic axons is associated with changes in dopamine-sensitive adenylate cyclase and dopamine receptor density in the partially denervated olfactory tubercle. The results indicate that dopamine- and NaF-stimulated adenylate cyclase activity increased as early as 7 d, while forskolin-sensitive activity increased at 3 d and persisted up to 20 d after lesioning; higher levels of GTP- and NaF- stimulated enzyme activity were found in detergent extracts of olfactory tubercle membranes from 20 d lesioned rats; higher levels of 3H-forskolin binding were found in membranes from 14 and 20 d lesioned rats; and there was an increase in dopamine receptor density, but not affinity, in olfactory tubercle membranes from lesioned rats. The data indicate that lesion-induced dopaminergic sprouting in the olfactory tubercle is temporally coordinated with the increased formation of dopamine receptors, both D1 and D2, the stimulatory guanine nucleotide regulatory protein (Ns) and the catalytic subunit (C) of adenylate cyclase in the postsynaptic membrane.

A role for 2-arachidonoylglycerol and endocannabinoid signaling in the locomotor response to novelty induced by olfactory bulbectomy

“…The OBX model has consequently been described as a model of dopaminergic dysfunction [20,21,23,26,39]. The modulatory role of endocannabinoids at the interface between glutamatergic, GABAergic and dopaminergic function was, therefore, investigated by comparing locomotor behavior, endocannabinoid levels and cannabinoid receptor densities in OBX and sham-operated rats.…”

“…Olfactory bulbectomy (OBX) deafferents the ventral striatum, thereby altering dopaminergic regulation throughout the striatum. OBX increases striatal tyrosine hydroxylase and dopamine receptor levels, induces sprouting of dopaminergic axons [20,21] and enhances sensitivity to the catecholamine reuptake inhibitor cocaine [22]. Recent work in our laboratories documents that OBX increases striatal dopamine overflow [23] and increases locomotor responsivity to the indirect dopamine agonist amphetamine [24].…”

Neurochemical and Behavioural Changes in Rat Models of Depression

“…It has been reported that OBX increases DA D1 and D2 receptor expression and DA mediated adenylate cyclase activity in the olfactory tubercle (OT). 73 DA has also been implicated in antidepressant treatments, including electro convulsive shock therapy (ECS). Acute ECS increases striatal concentrations of DOPAC [dihydroxyphenylacetic acid] and HVA, but chronic ECS decreases these metabolites.…”

Endocannabinoid modulation of amphetamine sensitization is disrupted in a rodent model of lesion‐induced dopamine dysregulation

“…In addition, olfactory bulbectomized rats exhibit faster acquisition of amphetamine self-administration relative to sham rats (Holmes et al, 2002). Olfactory bulbectomy induces sprouting of dopaminergic axons in the ventral striatum, in which basal dopamine release and dopamine receptor levels are increased at behaviorally relevant time points (Gilad and Reis, 1979;Holmes, 1999;Lingham and Gottesfeld, 1986;Masini et al, 2004). The olfactory bulbectomized (OBX) rat thus serves as a model of dopaminergic hyperfunction.…”