Rewarding electrical brain stimulation: Similar thresholds for flinders sensitve line hypercholinergic and flinders resistant line hypocholinergic rats

Abstract

Flinders Sensitive Line hypercholinergic rats, which exhibit augmented hypothermic responses to the cholinesterase inhibitor physostigmine and to the muscarinic agonist oxotremorine, have been proposed to represent a useful animal model for some aspects of human depression. With disturbance of reward processes considered to be a core feature of depression, the present studies were designed to investigate the neuropharmacology of brain stimulation-reward (BSR) in Flinders Sensitive Line (FSL) rats, Flinders Resistant Line (FRL) rats, and outbred control Sprague-Dawley rats. All animals were tested in a rate-free, current-threshold brain stimulation-reward paradigm, following acute challenges with the monoamine reuptake inhibitor cocaine, the dopamine D, receptor antagonist SCH-23390, the cholinergic muscarinic antagonist scopolamine, and the serotonin reuptake inhibitor fluoxetine. Baseline BSR thresholds did not differ across the three groups. For all groups, cocaine lowered thresholds, SCH-23390 and scopolamine-elevated thresholds, while fluoxetine had no significant effect. Thresholds for the three groups were not differentially affected by pharmacological challenge. Additionally, both Flinders Sensitive and Flinders Resistant Line rats exhibited diminished levels of locomotor activity relative to outbred Sprague-Dawley controls. These results suggest that both Flinders lines exhibit behavioral differences from outbred control rats, but not with regard to reward processes as assessed by rewarding electrical stimulation of the lateral hypothalamus.