Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Kupferschmidt DA

PROVIDER: S-EPMC3041248 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Kupferschmidt David A DA Lovejoy David A DA Rotzinger Susan S Erb Suzanne S

British journal of pharmacology 20110201 3

<h4>Background and purpose</h4>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 TCA ...[more]

PMID: 20883474

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Project description:The ability of many drugs of abuse, including cocaine, to mediate reinforcement and drug-seeking behaviors is in part mediated by the corticotropin-releasing hormone (CRH) system, in which CRH exerts its effects partly via the CRH receptor subtype 1 (CRHR1) in extra-hypothalamic areas. In fact, CRHR1 expressed in regions of the mesolimbic dopamine (DA) system have been demonstrated to modify cocaine-induced DA release and alter cocaine-mediated behaviors. Here we examined the role of neuronal selectivity of CRHR1 within the mesolimbic system on cocaine-induced behaviors. First we used a transgenic mouse line expressing GFP under the control of the Crhr1 promoter for double fluorescence immunohistochemistry to demonstrate the cellular location of CRHR1 in both dopaminergic and D1 dopaminoceptive neurons. We then studied cocaine sensitization, self-administration, and reinstatement in inducible CRHR1 knockouts using the CreERT2/loxP in either dopamine transporter (DAT)-containing neurons (DAT-Crhr1) or dopamine receptor 1 (D1)-containing neurons (D1-Crhr1). For sensitization testing, mice received five daily injections of cocaine (15 mg/kg IP). For self-administration, mice received eight daily 2 h cocaine (0.5 mg/kg per infusion) self-administration sessions followed by extinction and reinstatement testing. There were no differences in the acute or sensitized locomotor response to cocaine in DAT-Crhr1 or D1-Crhr1 mice and their respective controls. Furthermore, both DAT-Crhr1 and D1-Crhr1 mice reliably self-administered cocaine at the level of controls. However, DAT-Crhr1 mice demonstrated a significant increase in cue-induced reinstatement relative to controls, whereas D1-Crhr1 mice demonstrated a significant decrease in cue-induced reinstatement relative to controls. These data demonstrate the involvement of CRHR1 in cue-induced reinstatement following cocaine self-administration, and implicate a bi-directional role of CRHR1 for cocaine craving.

Dataset Information

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

Background and purpose

Experimental approach

Key results

Conclusions and implications

Publications

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

Similar Datasets

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