Pharmacological assessment of the relationship between cue properties and rewarding effects of electrical stimulation of the ventral tegmental area
Creators: name: Druhan, Jonathan Peter
Publisher: name: University of British Columbia
Year: 2010

description: The present series of experiments was designed to assess the utility of a discrimination procedure for measuring the affective properties of rewarding brain-stimulation. If the rewarding and discriminative stimulus properties of electrical brain stimulation were related, they may share a common substrate and be affected similarly by the same pharmacological manipulations. In Experiment 1, a discrimination procedure was developed to measure the cue properties of EBS delivered to the ventral tegmental area (VTA). Rats with VTA electrodes were trained to obtain food pellets by making a discriminated operant response on one of two levers following pulses of high intensity stimulation, or on the alternate lever after low intensity pulses. Following training, the rats were given tests in which generalized responding to intermediate intensities was measured. These tests were repeated either with conditions kept constant, or with the absolute intensities of the cues delivered within a sesion increased or decreased relative to baseline. The tests with higher or lower intensity ranges were intended to mimic the conditions that might prevail if the perceived intensities of the EBS were modified by drugs. The results of this experiment indicated that generalization gradients remained stable across three tests with conditions kept constant. When higher or lower current ranges were delivered, the discriminated responses were appropriately biased towards one lever or the other, resulting in lateral shifts in the generalization gradients. These results verified that the discrimination procedure provided a stable measure of the EBS stimulus properties, and that this measure was sensitive to changes in the intensities of the cues. In Experiment 2, tests for EBS generalization and self-stimulation (ICSS) were given after injections of vehicle, d-amphetamine (1.0 mg/kg and 2.0 mg/kg) and haloperidol (.075 mg/kg and .10 mg/kg). The results indicated that these doses of amphetamine and haloperidol did not affect the EBS generalization. However, during ICSS sessions, 2.0 mg/kg amphetamine decreased threshold and increased rates for ICSS whereas .10 mg/kg haloperidol resulted in an increase in threshold. These results suggest a dissociation of the stimulus properties of EBS from the DA reward substrate. In Experiment 3, the rats were tested for generalization after injections of physostigmine (.25 mg/kg and .50 mg/kg), scopolamine (.10 mg/kg and .25 mg/kg) and vehicle. Only the high dose of physostigmine (.50 mg/kg) produced significant differences in responding in this experiment. After injection of this drug, lower intensity stimuli elicited responding on the lever appropriate for the high current intensity, indicating a possible augmentation of the stimulus property of a fixed intensity of brain stimulation. The results of this study indicate that the cue properties of VTA brain-stimulation are dissociable from EBS reward related to the activation of DA neurons. However, evidence is provided which suggests that cholinergic neurons may be involved in the mediation of the EBS cues. In as much as cholinergic neurons are also involved in the rewarding effects of VTA brain-stimulation, these results may indicate a relationship between the cue properties of VTA EBS and an acetylcholine reward system.