Teneurin C-terminal associated peptide-1 blocks the effects of corticotropin-releasing factor on reinstatement of cocaine seeking and on cocaine-induced behavioural sensitization.
OBJECTIVE
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.


METHODS
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.).


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
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.
Kupferschmidt
David A
DA
Centre for the Neurobiology of Stress, Department of Psychology, University of Toronto Scarborough, Toronto, Ontario, Canada.
Lovejoy
David A
DA
Rotzinger
Susan
S
Erb
Suzanne
S
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage* / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D012646:Self Administration
D018765:Dopamine Uptake Inhibitors; D009419:Nerve Tissue Proteins; C500186:TCAP-1 protein, mouse; D003346:Corticotropin-Releasing Hormone; D003042:Cocaine