A limited role for ghrelin in heroin self‐administration and food deprivation‐induced reinstatement of heroin seeking in rats

Maric, Tia; Sedki, Firas; Ronfard, Benedicte; Chafetz, Danielle; Shalev, Uri

doi:10.1111/j.1369-1600.2011.00396.x

Cited by 40 publications

(34 citation statements)

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“…An implication of this study is that high plasma ghrelin levels may predispose to relapse in persons formerly addicted to cocaine. A similar effect was noted in a report from Shalev's group in which intracerebroventricular infusions of ghrelin (0.0, 1.5, and 3.0 ug/rat) produced increases in breakpoints on a progressive ratio schedule of heroin reinforcement (Maric et al, 2011). …”

Section: Role Of Ghrelin Receptors In Icss and Drug Self-administrationsupporting

confidence: 79%

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Ghrelin and ghrelin receptor modulation of psychostimulant action

Wellman¹,

Clifford²,

Rodríguez³

2013

Front. Neurosci.

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Ghrelin (GHR) is an orexigenic gut peptide that modulates multiple homeostatic functions including gastric emptying, anxiety, stress, memory, feeding, and reinforcement. GHR is known to bind and activate growth-hormone secretagogue receptors (termed GHR-Rs). Of interest to our laboratory has been the assessment of the impact of GHR modulation of the locomotor activation and reward/reinforcement properties of psychostimulants such as cocaine and nicotine. Systemic GHR infusions augment cocaine stimulated locomotion and conditioned place preference (CPP) in rats, as does food restriction (FR) which elevates plasma ghrelin levels. Ghrelin enhancement of psychostimulant function may occur owing to a direct action on mesolimbic dopamine function or may reflect an indirect action of ghrelin on glucocorticoid pathways. Genomic or pharmacological ablation of GHR-Rs attenuates the acute locomotor-enhancing effects of nicotine, cocaine, amphetamine and alcohol and blunts the CPP induced by food, alcohol, amphetamine and cocaine in mice. The stimulant nicotine can induce CPP and like amphetamine and cocaine, repeated administration of nicotine induces locomotor sensitization in rats. Inactivation of ghrelin circuit function in rats by injection of a ghrelin receptor antagonist (e.g., JMV 2959) diminishes the development of nicotine-induced locomotor sensitization. These results suggest a key permissive role for GHR-R activity for the induction of locomotor sensitization to nicotine. Our finding that GHR-R null rats exhibit diminished patterns of responding for intracranial self-stimulation complements an emerging literature implicating central GHR circuits in drug reward/reinforcement. Finally, antagonism of GHR-Rs may represent a smoking cessation modality that not only blocks nicotine-induced reward but that also may limit weight gain after smoking cessation.

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Section: Role Of Ghrelin Receptors In Icss and Drug Self-administrationsupporting

confidence: 79%

“…Additional studies are required to confirm these observations and to demonstrate that GHR-R antagonists can promote smoking abstinence. It is likely that modulation of GHR-Rs may be of use for other drugs of abuse, such as cocaine, alcohol and heroin (Jerlhag et al, 2009, 2010; Maric et al, 2011). …”

Section: Discussionmentioning

confidence: 99%

Ghrelin and ghrelin receptor modulation of psychostimulant action

Wellman¹,

Clifford²,

Rodríguez³

2013

Front. Neurosci.

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“…However, the involvement of ghrelin in cocaine seeking and taking might not be easily generalized to other drugs. Treatment with a ghrelin antagonist did not impair food deprivation-induced reinstatement of heroin seeking, although central infusions of ghrelin did increase the breakpoints on a progressive ratio schedule of heroin reinforcement (Maric et al, 2011). It is critical to note that the aforementioned study used acute food deprivation in a reinstatement of extinguished drug seeking procedure, which as mentioned above, might involve different brain mechanisms than prolonged food restriction in rats under withdrawal.…”

Section: Discussionmentioning

confidence: 99%

Is it stress? The role of stress related systems in chronic food restriction-induced augmentation of heroin seeking in the rat

Sedki¹,

Abbas²,

Angelis³

et al. 2013

Front. Neurosci.

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Drug addiction is a chronic disease characterized by recurring episodes of abstinence and relapse. The precise mechanisms underlying this pattern are yet to be elucidated, but stress is thought to be a major factor in relapse. Recently, we reported that rats under withdrawal and exposed to a mild chronic stressor, prolonged food restriction, show increased heroin seeking compared to sated controls. Previous studies demonstrated a critical role for corticotropin-releasing factor (CRF) and corticosterone, hormones involved in the stress response, in acute food deprivation-induced reinstatement of extinguished drug seeking. However, the role of CRF and corticosterone in chronic food restriction-induced augmentation of drug seeking remains unknown. Here, male Long-Evans rats were trained to self-administer heroin for 10 days in operant conditioning chambers. Rats were then removed from the training chambers, and subjected to 14 days of unrestricted (sated rats) or a mildly restricted (FDR rats) access to food, which maintained their body weight (BW) at 90% of their baseline weight. On day 14, different groups of rats were administered a selective CRF1 receptor antagonist (R121919; 0.0, 20.0 mg/kg; s.c.), a non-selective CRF receptor antagonist (α-helical CRF; 0.0, 10.0, 25.0 μg/rat; i.c.v.) or a glucocorticoid receptor antagonist (RU486; 0.0, 30.0 mg/kg; i.p.), and underwent a 1 h drug seeking test under extinction conditions. An additional group of rats was tested following adrenalectomy. All FDR rats showed a statistically significant increase in heroin seeking compared to the sated rats. No statistically significant effects for treatment with α-helical CRF, R121919, RU486 or adrenalectomy were observed. These findings suggest that stress may not be a critical factor in the augmentation of heroin seeking in food-restricted rats.

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“…Indeed, it has been shown that central administration of ghrelin enhanced the motivation to self‐administer heroin (Maric et al . ), and antagonism of GHSRs reduced the behavioural response to psychostimulants and nicotine (Jerlhag et al . ; Wellman et al .…”

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confidence: 97%

The role of ghrelin in drug and natural reward

Vengeliene

2013

Addiction Biology

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Ghrelin is a protein that has been given special attention in both nutrition and addiction research during the last decade. Consequently, a vast amount of information has been accumulated concerning the role of ghrelin in natural and drug reward. We are now in the position to ask whether the ghrelin system could be targeted to treat maladaptive behaviours such as obesity and drug addiction. Indeed, ghrelin research has demonstrated that blocking the activity of ghrelin receptors may be effective in reducing the consumption of both food and drugs of abuse. This review will give a short overview of our current knowledge about the ghrelin system in the context of drug and natural rewards as well as the possibility of developing potential ghrelin-based treatments.

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A limited role for ghrelin in heroin self‐administration and food deprivation‐induced reinstatement of heroin seeking in rats

Cited by 40 publications

References 45 publications

Ghrelin and ghrelin receptor modulation of psychostimulant action

Ghrelin and ghrelin receptor modulation of psychostimulant action

Is it stress? The role of stress related systems in chronic food restriction-induced augmentation of heroin seeking in the rat

The role of ghrelin in drug and natural reward

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