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ERK signaling and amphetamine-induced potentiation of conditioned cue effects on reward seeking

Mauna, Jocelyn (2013) ERK signaling and amphetamine-induced potentiation of conditioned cue effects on reward seeking. Master's Thesis, University of Pittsburgh. (Unpublished)

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Reward-seeking behaviors can be potentiated by exposure to cues that have been paired with a reward. This phenomenon is called Pavlovian instrumental transfer (PIT). PIT-like effects are thought to contribute to relapse of drug intake upon exposure to drug-associated cues. PIT was shown to be enhanced by prior exposure to psychostimulants; however, the molecular mechanisms involved are unknown. We previously found that extracellular signal-regulated kinase (ERK) activation within the nucleus accumbens (NAc) critical for PIT. Here we examine a possible involvement of NAc ERK signaling in the potentiation of PIT by prior exposure to psychostimulants. Rats underwent Pavlovian conditioning to associate a tone with food delivery, then underwent instrumental training to press a lever for food, and finally were tested for PIT. After each Pavlovian session half of the rats were treated with amphetamine (1mg/kg; i.p.) and the rest with saline (1ml/kg; i.p.). Some rats received Pavlovian conditioning only to assess the effect of prior amphetamine exposure specifically on cue-evoked ERK activation in the NAc. To determine the importance of timing of amphetamine exposure in relation to the Pavlovian conditioning training, some rats were treated with drug or saline 6 hrs after the daily session. Amphetamine treatment after daily Pavlovian training increased cue-evoked NAc ERK activation, without affecting basal ERK activation or discriminative food cup approach. Amphetamine exposure caused a marked increase in PIT accompanied by an increase in cue-evoked ERK activation. There were no drug effects on basal lever pressing, inactive lever pressing, or discriminative food cup approach during the PIT test. The effect of prior amphetamine exposure on cue-evoked NAc ERK activation and PIT were observed when amphetamine was administered immediately after the daily Pavlovian conditioning but not when it was administered 6 hrs later. These findings are consistent with a role for cue-evoked NAc ERK activation in the enhancement of PIT observed days after repeated exposure to amphetamine. Potentiation dependence on the timing of amphetamine administration relative to Pavlovian conditioning argues against an explanation in terms of general sensitization but instead suggests a drug effect on the consolidation of the cue-reward association.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Mauna, Jocelynjdm54@pitt.eduJDM54
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSved, Alan Fsved@pitt.eduSVED
Committee MemberThiels, Eddathiels@pitt.eduTHIELS
Committee MemberSesack, Susansesack@pitt.eduSESACK
Date: 26 September 2013
Date Type: Publication
Defense Date: 6 August 2013
Approval Date: 26 September 2013
Submission Date: 16 August 2013
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 57
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Neuroscience
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Memory Pavlovian Instrumental Psychostimulant Extracellular signal-regulated kinase
Date Deposited: 27 Sep 2013 00:01
Last Modified: 26 Sep 2018 05:15


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