Spatial learning in rats is impaired by microinfusions of protein kinase C-γ antisense oligodeoxynucleotide within the nucleus accumbens

• Published in: Neurobiology of learning and memory 2004-03, Vol.81 (2), p.120-136
• Main Authors: Alvarez-Jaimes, Lily, Betancourt, Elba, Centeno-González, Marjorie, Feliciano-Rivera, Mara Z., Rodrı́guez, Danella, Ortı́z, Sandra Peña de, Maldonado-Vlaar, Carmen S.
• Format: Article
• Language: English
• Subjects: Animal; Animals; Antisense oligodeoxynucleotide; Biological and medical sciences; Cognition Disorders - chemically induced; Food search spatial learning task; Fundamental and applied biological sciences. Psychology; Immunoblotting; Learning - drug effects; Learning. Memory; Male; Memory; Microinjections; Nucleus accumbens; Nucleus Accumbens - drug effects; Oligodeoxyribonucleotides, Antisense - administration & dosage; Oligodeoxyribonucleotides, Antisense - adverse effects; Oligodeoxyribonucleotides, Antisense - pharmacology; PKC expression and activity; PKC-γ; Protein Kinase C - administration & dosage; Protein Kinase C - adverse effects; Protein Kinase C - pharmacology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Long-Evans; Space Perception - drug effects; Spatial learning
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1016/j.nlm.2003.12.001

The nucleus accumbens (NAcc) has been shown to play a role in motor and spatial learning. Protein kinase C (PKC) has been implicated in the mechanisms of initiation and maintenance of long-term potentiation that is thought to be involved in the storage of long-term memory. In the present study, the importance of de novo synthesis of PKC-γ within the NAcc in the acquisition and retention of spatial discrimination learning was assessed using an antisense knockdown approach. Separate groups of Long–Evans rats were exposed to acute microinfusions (6 μg/μl) of PKC-γ antisense oligodeoxynucleotide (AS-ODN), control oligodeoxynucleotide (C-ODN) or vehicle into the NAcc at 24 and 3 h before each training session. Behavioral findings showed that the blockade of NAcc-PKC-γ translation caused impairments in the early phase of learning and retention of spatial information. Biochemical experiments showed that PKC-γ expression was reduced and Ca 2+/phospholipid-dependent protein kinase C (PKC) activity was blocked significantly in the AS-ODN-treated rats in comparison with control rats. The present findings suggest that NAcc-PKC-γ plays a role during the early acquisition of spatial learning. Also, retention test results suggest that NAcc-PKC-γ may be working as an intermediate factor involved in the onset of molecular mechanisms necessary for spatial memory consolidation within the NAcc.