This proposal addresses the hypothesis that behavioral tolerance to stimulant drugs is mediated by instrumental learning. Previous research has shown that amphetamine initially suppresses the ingestion of sweetened milk primarily by inducing stereotyped head movements, which interfere with feeding (Wolgin et al., 1987). We propose that tolerance to this effect involves learning to channel such movements into a more adaptive stereotyped response, namely, licking a drinking tube.
One aim of the proposed research is to determine whether tolerance develops when licking is precluded. Rats implanted with oral cannulas and given chronic injections of amphetamine will be reinforced with milk directly into their mouths for holding their heads stationary with or without the opportunity to lick an empty drinking tube.
A second aim i s to determine whether individual differences in motor activity evoked by an acute injection of amphetamine are correlated with the rate and/or level of tolerance that subsequently develops to the hypophagic effect of the drug.
A third aim i s to assess the generality of the theory by determining whether tolerance to the hypophagic effect of apomorphine, cocaine, and methylphenidate also involves learning to channel stereotyped movements into licking. This will be accomplished by comparing the effect of each of these drugs on the milk intake and movement patterns of cannula- and bottle-fed rats.
A final aim of this proposal is to determine whether tolerance develops to the hypophagic effect of amphetamine when stereotyped movements do not contribute to hypophagia, i.e., in """"""""free feeding"""""""" cannula-fed rats. The relatively rapid development of tolerance to the behaviorally disruptive effects of stimulant drugs may contribute to their widespread abuse. To the extent that behavioral tolerance involves instrumental learning, the proposed research will provide a rationale for understanding how people adapt to the behaviorally disruptive effects of stimulant drugs of abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
2R01DA004592-04
Application #
3210331
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1990-03-01
Project End
1996-04-30
Budget Start
1993-05-01
Budget End
1994-04-30
Support Year
4
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Florida Atlantic University
Department
Type
Schools of Arts and Sciences
DUNS #
004147534
City
Boca Raton
State
FL
Country
United States
Zip Code
33431
Wolgin, David L; Munoz, James R (2006) Role of instrumental learning in tolerance to cathinone hypophagia. Behav Neurosci 120:362-70
Wolgin, David L; Jakubow, James J (2004) Tolerance to amphetamine hypophagia: a real-time depiction of learning to suppress stereotyped movements in the rat. Behav Neurosci 118:470-8
Wolgin, David L; Jakubow, James J (2003) Tolerance to amphetamine hypophagia: a microstructural analysis of licking behavior in the rat. Behav Neurosci 117:95-104
Hughes, K M; Wolgin, D L (2002) Changes in behavioural contingencies produce a loss of tolerance to amphetamine hypophagia in rats despite continued feeding tests while drugged. Behav Pharmacol 13:279-86
Wolgin, David L (2002) Effects of chronic amphetamine on the appetitive and consummatory phases of feeding. Appetite 38:221-3
Wolgin, D L; Hughes, K M (2001) Long-term retention of tolerance to amphetamine hypophagia following cessation of drug injections and feeding tests. Pharmacol Biochem Behav 70:367-73
Wolgin, D L (2000) Contingent tolerance to amphetamine hypophagia: new insights into the role of environmental context in the expression of stereotypy. Neurosci Biobehav Rev 24:279-94
Hughes, K M; Popi, L; Wolgin, D L (1999) Loss of tolerance to amphetamine-induced hypophagia in rats: homeostatic readjustment vs. instrumental learning. Pharmacol Biochem Behav 64:177-82
Hughes, K M; Popi, L; Wolgin, D L (1998) Experiential constraints on the development of tolerance to amphetamine hypophagia following sensitization of stereotypy: instrumental contingencies regulate the expression of sensitization. Psychopharmacology (Berl) 140:445-9
Wolgin, D L; Hughes, K M (1997) Role of behavioral and pharmacological variables in the loss of tolerance to amphetamine hypophagia. Psychopharmacology (Berl) 132:342-9

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