Selective serotonin receptor stimulation of the ventral tegmentum differentially affects appetitive motivation for sugar on a progressive ratio schedule of reinforcement.

Serotonin signaling influences satiety and motivation through known actions in the hindbrain and hypothalamus. Recently, we reported that some classes of serotonin receptors also modulate food intake through actions in the ventral tegmentum and the nucleus accumbens. In the current experiments, we examined whether activation or blockade of individual serotonin receptor subtypes in the ventral tegmentum might also affect appetitive motivation for sugar pellets as assessed in a progressive ratio (PR) task. Separate groups of rats were tested following stimulation or blockade of ventral tegmental serotonin 1A, 1B, 2A, 2B, 2C, or 3 receptors. Rats within each group received multiple doses of a single drug across days; each test was separated by 72 h. Progressive ratio break point was significantly affected by stimulation of ventral tegmental serotonin 1A receptors with 8-OH-DPAT (0, 2, 4, 8 µg/side) or stimulation of serotonin 3 receptors with mCPBG (0, 10, & 20 µg/side). High doses of both agents tended to decrease break point. Additionally, stimulation of serotonin 2C receptors with RO60-0175 (at 0, 2, and 5 µg/side) reduced total lever presses and demonstrated a trend towards reducing break point. There were no effects of stimulating ventral tegmental serotonin 1B, 2A, or 2B receptors on break point; neither did antagonism of any of the serotonin receptor subtypes significantly affect performance. These data provide additional evidence that serotonergic signaling in the mesolimbic pathway affects motivated behavior, and demonstrate that a subset of serotonin receptors impact not only food consumption, but appetitive food-seeking as well.

A systematic investigation of the differential roles for ventral tegmentum serotonin 1- and 2-type receptors on food intake in the rat.

Central serotonin (5-HT) pathways are known to influence feeding and other ingestive behaviors. Although the ventral tegmentum is important for promoting the seeking and consumption of food and drugs of abuse, the roles of 5-HT receptor subtypes in this region on food intake have yet to be comprehensively examined. In these experiments, food restricted rats were given 2-h access to rat chow; separate groups of non-restricted animals had similar access to a sweetened fat diet. Feeding and locomotor activity were monitored following ventral tegmentum stimulation or blockade of 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, or 5-HT2C receptors. 5-HT1A receptor stimulation transiently inhibited rearing behavior and chow intake in food-restricted rats, and had a biphasic effect on non-restricted rats offered the palatable diet. 5-HT1B receptor agonism transiently inhibited feeding in restricted animals, but did not affect intake of non-restricted rats. In contrast, 5-HT1B receptor antagonism decreased palatable feeding. Although stimulation of ventral tegmental 5-HT2B receptors with BW723C86 did not affect hunger-driven food intake, it significantly affected palatable feeding, with a trend for an increasing intake at 2.0µg/side but not at 5.0µg/side. Antagonism of the same receptor modestly but significantly inhibited feeding of the palatable diet at 5.0µg/side ketanserin. Neither stimulation nor blockade of 5-HT2A or 5-HT2C receptors caused prolonged effects on intake or locomotion. These data suggest that serotonin's effects on feeding within the ventral tegmentum depend upon the specific receptor targeted, as well as whether intake is motivated by food restriction or the palatable nature of the offered diet.

Reward circuit DBS improves Parkinson's gait along with severe depression and OCD.

A 59-year-old Caucasian man with a past history of Parkinson's disease (PD) status post-bilateral subthalamic nucleus (STN) deep brain stimulation (DBS), who also had treatment-resistant (TR) obsessive-compulsive disorder (OCD), and treatment-resistant depression (TRD), presented for further evaluation and management of his TR OCD. After an unsuccessful attempt to treat his OCD by reprogramming his existing STN DBS, he was offered bilateral ventral capsule/ventral striatum (VC/VS) DBS surgery. In addition to the expected improvement in OCD symptoms, he experienced significant improvement in both PD-related apathy and depression along with resolution of suicidal ideation. Furthermore, the patient's festinating gait dramatically improved. This case demonstrates that DBS of both the STN and VC/VS appears to have an initial signal of safety and tolerability. This is the first instance where both the STN and the VC/VS DBS targets have been implanted in an individual and the first case where a patient with PD has received additional DBS in mood-regulatory circuitry.