Dose responses for drugs were selected from your literature (Hayes food intake, weights of food hoppers were recorded to the nearest 0.1?g and food spillage was accounted for in cumulative intake measurements. Effect of Intra-VTA Amylin Receptor Activation on Chow Intake and Meal Patterns Chow-maintained rats were housed in a custom-made automated feedometer system consisting of hanging wire mesh cages with a small access hole leading to a food cup resting on an electronic scale. or vehicle (100?nl aCSF). Food and kaolin intake, as well as spillage of both substances, were ATF3 measured at 24?h; BW switch over the 24-h period was also recorded. Effect of Intra-VTA Amylin Receptor Activation or Blockade on Locomotor Activity Rats (axis. The first 30?min of data from each phase of screening (pre-injection/baseline and post injection) were discarded to avoid adding variability to the data as a result of the transient increased locomotor activity observed as a result of animal handling (Skibicka Sucrose Intake Rats (access to lab chow (Harlan Teklad, Frederick, MD, USA) in their home cages throughout MARK4 inhibitor 1 the first phase of behavioral screening. After 7 days of FR5 responding, rats received unilateral VTA injections of sCT (0.04?g) or vehicle (100?nl aCSF). VTA injections were given 2?h after the onset of the light phase. The effects of the drug on sucrose self-administration on a progressive ratio (PR) schedule of reinforcement were evaluated. Under a PR routine, the response requirement for each subsequent delivery of a sucrose pellet increases exponentially until the subject fails to meet a requirement. In the current experiments, the response requirement for the level for all those assessments MARK4 inhibitor 1 was set at analyses. For operant studies, two-tailed paired analyses, analyses, 0.4 and 0.04?g different from vehicle (comparison of vehicle 0.4?g sCT, comparison of vehicle to 0.04?g sCT, comparison, 0.4?g sCT different from all other doses (0.4?g sCT significant (0.4?g sCT, 0.04 or 0.4?g, 0.4?g, sCT, AC187, 0.04?g sCT significant (0.01?g sCT significant (comparison of vehicle 0.04?g sCT, comparison of vehicle 0.04?g sCT, comparison of vehicle 0.04?g sCT, 0.17 or 0.3?g, comparison indicates significant difference from all other treatments (comparisons between vehicle and 5?g/kg sCT, comparisons between vehicle and 5?g/kg sCT, amylin, as blockade of VTA amylin receptors by the antagonist AC187 increased food intake. Interestingly, intra-VTA AC187 experienced only a very brief, transient effect on locomotor activity. Given that intra-VTA sCT also experienced only minimal and transient effects on locomotor activity, it appears that changes in VTA amylin receptor activity selectively alter feeding and have relatively little impact on locomotor function. An additional noteworthy obtaining of the current studies is the fact that selective blockade of VTA amylin receptors by AC187 attenuated the intake-suppressive effects of a peripherally administered amylin receptor agonist. Given that amylin can penetrate the bloodCbrain barrier (Banks food-restricted rats, respectively: active lever presses, 44% 34% pellets earned, 28% 14% break point, 38% 31%). These slight differences may be due to the additional motivation to obtain food produced by chronic food deprivation. Together, these findings suggest that VTA amylin receptor activation may reduce food-directed motivational processes. Whether VTA amylin receptor signaling contributes to the expression of other non-food-oriented appetitive behaviors is an interesting hypothesis that requires further investigation. Until now, the AP has been viewed as the primary site of action for the intake-suppressive effects of amylin. Numerous papers clearly establish the AP as an important amylin-responsive site (Lutz VTA amylin receptor populations may help to explain the disparate time courses of feeding effects obtained after AP VTA amylin receptor activation (Mollet et al, 2004); this is MARK4 inhibitor 1 an intriguing possibility that should be tested empirically. Given the important role of mesolimbic dopamine signaling in the regulation of feeding (Narayanan et al, 2010; Vucetic and Reyes, 2010), VTA amylin-induced alterations in dopamine production or release may also mediate the feeding effects observed in the present studies, but this too remains to be.