Spatial learning in rats is impaired by microinfusions of protein kinase C-gamma antisense oligodeoxynucleotide within the nucleus accumbens.
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-gamma 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 (6microg/microl) of PKC-gamma antisense oligodeoxynucleotide (AS-ODN), control oligodeoxynucleotide (C-ODN) or vehicle into the NAcc at 24 and 3h before each training session. Behavioral findings showed that the blockade of NAcc-PKC-gamma translation caused impairments in the early phase of learning and retention of spatial information. Biochemical experiments showed that PKC-gamma 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-gamma plays a role during the early acquisition of spatial learning. Also, retention test results suggest that NAcc-PKC-gamma may be working as an intermediate factor involved in the onset of molecular mechanisms necessary for spatial memory consolidation within the NAcc.
Department of Biology, University of Puerto Rico, Río Piedras Campus, P.O. Box 23360, San Juan 00931-3360, Puerto Rico.
Lily
L
Alvarez-Jaimes
Elba
E
Betancourt
Marjorie
M
Centeno-González
Mara Z
MZ
Feliciano-Rivera
Danella
D
Rodríguez
Sandra
S
Peña de Ortíz
Carmen S
CS
Maldonado-Vlaar
D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced; D015151:Immunoblotting; D007858:Learning / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D009714:Nucleus Accumbens / Q000187:drug effects*; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011493:Protein Kinase C / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D013028:Space Perception / Q000187:drug effects*
D020319:Oligodeoxyribonucleotides, Antisense; C087857:protein kinase C gamma; D011493:Protein Kinase C