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Updated: Dec 10, 2025

Pavlovian Conditioned Approach Training in Rats
Published on: February 4, 2016
CaMKII antagonism in the ventral tegmental area impairs acquisition of conditioned approach learning in rats
Rudolf Nisanov1, Eva Schelbaum2, Debra Morris2
1Graduate Center, City University of New York, 365 Fifth Avenue, New York, NY 10016, USA.
Abstract:
This study investigated the role of calcium2+/calmodulin-dependent protein kinase II (CaMKII), a protein in the second messenger pathway of NMDA receptors, in the ventral tegmental area (VTA) in the acquisition and performance of conditioned approach learning. Male Long-Evans rats (N = 79) were exposed to 3 (to test acquisition) or 7 (to test performance) conditioning sessions in which they received 30 paired presentations of a light stimulus (CS) and a food pellet (US) on a random time schedule. These conditioning sessions were then followed by one 30-min session without the CS or US and lastly by a CS-only test session, where only the light stimulus was presented (without food) according to the same schedule as the conditioning sessions. Bilateral intra-VTA injections of KN93 (vehicle, 3.0, 4.5 or 6.0 μg/0.5 μL), a CaMKII inhibitor, were administered prior to each conditioning session to test effects on the acquisition of conditioned approach or prior to the CS-only test session to test effects on the performance of conditioned approach. KN93, when given prior to conditioning sessions, significantly reduced the number of conditioned approach responses emitted during CS presentations in the CS-only test. When KN93 was given prior to the CS-only test it had no effect. These results suggest that CaMKII activation in the VTA is necessary for the acquisition, but not the performance, of reward-related learning.
Insights
Calcium/calmodulin-dependent protein kinase II (CaMKII) in the ventral tegmental area (VTA) is crucial for acquiring reward-related learning. CaMKII inhibition impaired learning acquisition but not performance in rats.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
Background:
- The ventral tegmental area (VTA) is a key brain region involved in reward processing and motivation.
- NMDA receptor signaling pathways, including calcium/calmodulin-dependent protein kinase II (CaMKII), play critical roles in synaptic plasticity and learning.
Purpose of the Study:
- To investigate the role of CaMKII in the VTA during the acquisition and performance of conditioned approach learning.
- To determine if CaMKII inhibition affects the initial learning of reward associations or the retrieval of learned behaviors.
Main Methods:
- Male Long-Evans rats underwent conditioning sessions involving paired light (CS) and food (US) stimuli.
- Bilateral intra-VTA injections of a CaMKII inhibitor (KN93) were administered before conditioning (acquisition) or before testing (performance).
- Conditioned approach responses were measured during a stimulus-only test session.
Main Results:
- Inhibiting CaMKII in the VTA before conditioning significantly reduced conditioned approach responses during testing.
- Administering the CaMKII inhibitor before the test session did not affect the performance of learned approach behavior.
- These findings indicate a specific role for CaMKII in the VTA during the learning phase.
Conclusions:
- CaMKII activation within the VTA is essential for the acquisition of conditioned approach learning.
- CaMKII in the VTA is not required for the performance or expression of already acquired reward-related behaviors.
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