Pavlovian conditioned drug effects contribute importantly to critical drug abuse treatment issues of relapse and craving. Application of conditioning principles to treatment are complicated, however, by the fact that drug effects can be conditioned to a wide variety of exteroceptive environmental stimuli associated with drug use and that extinction procedures can only suppress but cannot eliminate the efficacy of the conditioned stimulus (CS) to elicit the conditioned response (CR). In this regard, it is well-established by tests of conditioned effects following extinction in both drug and non-drug models, that CS elicitation of the CR can be reinstated by startle and stress stimuli. Recently, we have found that caffeine could also reactivate an extinguished conditioned dopaminergic drug response. This linkage of caffeine to the modulation of CS efficacy in drug conditioning is important because it creates the possibility of developing a pharmacological identity of the neurochemical mechanisms which modulate conditioned drug effects. Thus, one objective of the present proposal is to relate the modulatory influence of caffeine on drug conditioning processes to caffeine mechanisms; e.g. to adenosine antagonism, norepinephrine release and GABAergic antagonism. Another objective is to examine the influence of over-the counter stimulant drugs (i.e., methylxanthines and phenylethylamines) on the reactivation of an extinguished conditioned dopaminergic drug response. Overall, the objective is to identify, using the unilateral 6-hydroxydopamine rotation and place preference animal models, drug treatments which can facilitate/antagonize CS-efficacy in conditioned drug responses induced by dopaminergic drugs and by drugs with high abuse liability such as amphetamine, cocaine and morphine. The results obtained can provide a basis for pharmacological treatment strategies for clinical control of craving and attendant relapse problems during drug abuse rehabilitation.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
2R01DA005366-04
Application #
3211699
Study Section
Drug Abuse Biomedical Research Review Committee (DABR)
Project Start
1987-09-30
Project End
1994-08-31
Budget Start
1990-09-30
Budget End
1991-08-31
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Upstate Medical University
Department
Type
Schools of Medicine
DUNS #
058889106
City
Syracuse
State
NY
Country
United States
Zip Code
13210
de Matos, Liana Wermelinger; Carey, Robert J; Carrera, Marinete Pinheiro (2010) Apomorphine conditioning and sensitization: the paired/unpaired treatment order as a new major determinant of drug conditioned and sensitization effects. Pharmacol Biochem Behav 96:317-24
Carey, Robert J; Damianopoulos, Ernest N; Shanahan, Arielle B (2009) Cocaine conditioning: reversal by autoreceptor dose levels of 8-OHDPAT. Pharmacol Biochem Behav 91:447-52
Carey, Robert J; Damianopoulos, Ernest N; Shanahan, Arielle B (2008) Cocaine conditioned behavior: a cocaine memory trace or an anti-habituation effect. Pharmacol Biochem Behav 90:625-31
Muller, C P; Carey, R J; Wilkisz, M et al. (2008) Acute anxiolytic effects of cocaine: the role of test latency and activity phase. Pharmacol Biochem Behav 89:218-26
Pum, M E; Carey, R J; Huston, J P et al. (2008) Role of medial prefrontal, entorhinal, and occipital 5-HT in cocaine-induced place preference and hyperlocomotion: evidence for multiple dissociations. Psychopharmacology (Berl) 201:391-403
Pum, M; Carey, R J; Huston, J P et al. (2007) Dissociating effects of cocaine and d-amphetamine on dopamine and serotonin in the perirhinal, entorhinal, and prefrontal cortex of freely moving rats. Psychopharmacology (Berl) 193:375-90
Muller, Christian P; Carey, Robert J; Huston, Joseph P et al. (2007) Serotonin and psychostimulant addiction: focus on 5-HT1A-receptors. Prog Neurobiol 81:133-78
Dias, Flavia Regina Cruz; Carey, Robert J; Carrera, Marinete Pinheiro (2006) Conditioned locomotion induced by unilateral intrastriatal administration of apomorphine: D(2) receptor activation is critical but not the expression of the unconditioned response. Brain Res 1083:85-95
Carey, Robert J; Damianopoulos, Ernest N (2006) Cocaine conditioning and sensitization: the habituation factor. Pharmacol Biochem Behav 84:128-33
Muller, Christian P; Carey, Robert J (2006) Intracellular 5-HT 2C-receptor dephosphorylation: a new target for treating drug addiction. Trends Pharmacol Sci 27:455-8

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