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Teneurin C‐terminal associated peptide‐1 blocks the effects of corticotropin‐releasing factor on reinstatement of cocaine seeking and on cocaine‐induced behavioural sensitization
Author(s) -
Kupferschmidt David A.,
Lovejoy David A.,
Rotzinger Susan,
Erb Suzanne
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.01055.x
Subject(s) - sensitization , self administration , addiction , psychology , pharmacology , neuropeptide , medicine , endocrinology , neuroscience , receptor
BACKGROUND AND PURPOSE The stress‐related neuropeptide, corticotropin‐releasing factor (CRF), has become an important focus of studies of cocaine addiction, and in particular, the effects of stress on cocaine‐related behaviours. A recently discovered peptide system, the teneurin C‐terminal associated peptides (TCAP), has been implicated in the regulation of the stress response, via a CRF‐related mechanism. Here we have determined whether treatment with TCAP‐1, a synthetic analogue of TCAP, modulated two cocaine‐related behaviours induced by CRF: reinstatement of cocaine seeking, and expression of cocaine‐induced behavioural sensitization. EXPERIMENTAL APPROACH In Experiment 1, rats trained to self‐administer cocaine were given acute or repeated (once daily for 5 days) i.c.v. injections of TCAP‐1 before tests for reinstatement in response to CRF (105 pmol, i.c.v.), intermittent footshock stress (0.9 mA), or cocaine (15 mg·kg −1 , i.p.). In Experiment 2, rats pre‐exposed to cocaine (15–30 mg·kg −1 , i.p.) or saline for 7 days were treated with TCAP‐1 (once daily for 5 days; i.c.v.) and subsequently tested for locomotor responses to CRF (105 pmol, i.c.v.) or cocaine (15 mg·kg −1 , i.p.). KEY RESULTS Five day pre‐exposure with TCAP‐1 blocked CRF‐, but not footshock‐ or cocaine‐induced reinstatement of cocaine seeking; acute pretreatment with TCAP‐1 was without effect in all test conditions. Similarly, repeated TCAP‐1 pre‐exposure blocked the cocaine‐sensitized locomotor response to CRF, but not to cocaine. CONCLUSIONS AND IMPLICATIONS Repeated TCAP‐1 exposure induced robust and selective inhibition of cocaine‐related behavioural responses to CRF, suggesting that TCAP‐1 may normalize signalling within CRF systems dysregulated by cocaine exposure.