The major goal of this proposed research is to characterize the cellular mechanisms underlying the effects of endogenous opioid peptide-containing systems on learning and memory processes. The theoretical context underlying these studies is based on the suggestion that the neuronal mechanism of memory storage has two fundamental components, a centrally located memory trace and a peripherally located modulatory input. We suggest that opioid peptide systems are involved both in forming memory traces and in modulating associative strength. This research project has relevance to drug abuse because drug craving and compulsive drug-seeking behavior are aroused by memories of the reinforcing drug experience, and they may be maintained by plasticity in opioid peptide-containing neuronal systems. Experiments are proposed to assess the generality of the involvement of the endogenous opioid peptides, [Leu)- and [Met]enkephalin, in modulation of learning processes by characterizing their effects on acquisition and retention of appetitively-motivated conditioning. Studies also will investigate the opioid receptor subtype(s) through which these effects are mediated and the location of these receptor(s) vis-a-vis the blood-brain barrier. Additional experiments will investigate the opioid receptor- dependence of long-term potentiation, a candidate mechanism for memory storage processes, in several pathways within the hippocampus in vivo, using both acute studies in anesthetized animals and longer-term investigations in awake, freely moving animals with chronically implanted electrodes.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA004195-09
Application #
2117062
Study Section
Drug Abuse Biomedical Research Review Committee (DABR)
Project Start
1987-01-01
Project End
1995-12-31
Budget Start
1995-06-01
Budget End
1995-12-31
Support Year
9
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Rodriguez, Jesse S; Boctor, Sherin Y; Flores, Luke C et al. (2011) Local pretreatment with the cannabinoid CB1 receptor antagonist AM251 attenuates methamphetamine intra-accumbens self-administration. Neurosci Lett 489:187-91
Achanta, Pragathi; Fuss, Martin; Martinez Jr, Joe L (2009) Ionizing radiation impairs the formation of trace fear memories and reduces hippocampal neurogenesis. Behav Neurosci 123:1036-45
Ricoy, Ulises M; Martinez Jr, Joe L (2009) Local hippocampal methamphetamine-induced reinforcement. Front Behav Neurosci 3:47
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Boctor, Sherin Y; Martinez Jr, Joe L; Koek, Wouter et al. (2007) The cannabinoid CB1 receptor antagonist AM251 does not modify methamphetamine reinstatement of responding. Eur J Pharmacol 571:39-43
Achanta, Pragathi; Thompson, Kenira J; Fuss, Martin et al. (2007) Gene expression changes in the rodent hippocampus following whole brain irradiation. Neurosci Lett 418:143-8
Hernandez, Ruben V; Navarro, Mary M; Rodriguez, Ward A et al. (2005) Differences in the magnitude of long-term potentiation produced by theta burst and high frequency stimulation protocols matched in stimulus number. Brain Res Brain Res Protoc 15:6-13
Thompson, Kenira J; Mata, Mario L; Orfila, James E et al. (2005) Metabotropic glutamate receptor antagonist AIDA blocks induction of mossy fiber-CA3 LTP in vivo. J Neurophysiol 93:2668-73
Peng, Haixiang; Derrick, Brian E; Martinez Jr, Joe L (2004) Time-course study of SCG10 mRNA levels associated with LTP induction and maintenance in the rat Schaffer-CA1 pathway in vivo. Brain Res Mol Brain Res 120:182-7
Meilandt, William J; Barea-Rodriguez, Edwin; Harvey, Stephen A K et al. (2004) Role of hippocampal CA3 mu-opioid receptors in spatial learning and memory. J Neurosci 24:2953-62

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