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Ghrelin receptor antagonism attenuates cocaine- and amphetamine-induced locomotor stimulation, accumbal dopamine release, and conditioned place preference.

Jerlhag E, Egecioglu E, Dickson SL, Engel JA - Psychopharmacology (Berl.) (2010)

Bottom Line: As the target circuits for ghrelin in the brain include a mesolimbic reward pathway that is intimately associated with reward-seeking behaviour, we sought to determine whether the central ghrelin signaling system is required for reward from drugs of abuse other than alcohol, namely cocaine or amphetamine.We found that amphetamine-as well as cocaine-induced locomotor stimulation and accumbal dopamine release were reduced in mice treated with a GHS-R1A antagonist.Our data suggest that the central ghrelin signaling system constitutes a novel potential target for treatment of addictive behaviours such as drug dependence.

View Article: PubMed Central - PubMed

Affiliation: Section for Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, SE-405 30, Gothenburg, Sweden. elisabet.jerlhag@pharm.gu.se

ABSTRACT

Introduction: Recently we demonstrated that genetic or pharmacological suppression of the central ghrelin signaling system, involving the growth hormone secretagogue receptor 1A (GHS-R1A), lead to a reduced reward profile from alcohol. As the target circuits for ghrelin in the brain include a mesolimbic reward pathway that is intimately associated with reward-seeking behaviour, we sought to determine whether the central ghrelin signaling system is required for reward from drugs of abuse other than alcohol, namely cocaine or amphetamine.

Results: We found that amphetamine-as well as cocaine-induced locomotor stimulation and accumbal dopamine release were reduced in mice treated with a GHS-R1A antagonist. Moreover, the ability of these drugs to condition a place preference was also attenuated by the GHS-R1A antagonist.

Conclusions: Thus GHS-R1A appears to be required not only for alcohol-induced reward, but also for reward induced by psychostimulant drugs. Our data suggest that the central ghrelin signaling system constitutes a novel potential target for treatment of addictive behaviours such as drug dependence.

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Related in: MedlinePlus

Verification of probe placement. A coronal mouse brain section showing ten representative probe placements (vertical lines) in the NAcc of mice used in the present study (Franklin and Paxinos 1996). Ten representative placements are illustrated, but all other placements were within the NAcc shell. The probe is not shown to scale, and the outer diameter of the probe was 310 μm. Placements outside this area were not included in the statistical analysis. The number given in the brain section indicates millimeters anterior (+) from bregma
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Fig3: Verification of probe placement. A coronal mouse brain section showing ten representative probe placements (vertical lines) in the NAcc of mice used in the present study (Franklin and Paxinos 1996). Ten representative placements are illustrated, but all other placements were within the NAcc shell. The probe is not shown to scale, and the outer diameter of the probe was 310 μm. Placements outside this area were not included in the statistical analysis. The number given in the brain section indicates millimeters anterior (+) from bregma

Mentions: After the experiment, the location of the probe was verified and only mice with probe placement in the NAcc were included in the statistical analysis. It should also be emphasized that in a few mice, the probe was located outside the NAcc, and in these mice, no effect of amphetamine/cocaine on accumbal dopamine release was observed (Fig. 3). It should be emphasized that in a few mice, the probe was located outside the NAcc shell, and in these mice, no effect of amphetamine or cocaine on accumbal dopamine release was observed (data not shown). Given that only amphetamine and cocaine increase accumbal dopamine compared to vehicle, it appears less likely that the probes causes structural defects within the NAcc that may influence the possibility to detect dopamine release.Fig. 3


Ghrelin receptor antagonism attenuates cocaine- and amphetamine-induced locomotor stimulation, accumbal dopamine release, and conditioned place preference.

Jerlhag E, Egecioglu E, Dickson SL, Engel JA - Psychopharmacology (Berl.) (2010)

Verification of probe placement. A coronal mouse brain section showing ten representative probe placements (vertical lines) in the NAcc of mice used in the present study (Franklin and Paxinos 1996). Ten representative placements are illustrated, but all other placements were within the NAcc shell. The probe is not shown to scale, and the outer diameter of the probe was 310 μm. Placements outside this area were not included in the statistical analysis. The number given in the brain section indicates millimeters anterior (+) from bregma
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2908453&req=5

Fig3: Verification of probe placement. A coronal mouse brain section showing ten representative probe placements (vertical lines) in the NAcc of mice used in the present study (Franklin and Paxinos 1996). Ten representative placements are illustrated, but all other placements were within the NAcc shell. The probe is not shown to scale, and the outer diameter of the probe was 310 μm. Placements outside this area were not included in the statistical analysis. The number given in the brain section indicates millimeters anterior (+) from bregma
Mentions: After the experiment, the location of the probe was verified and only mice with probe placement in the NAcc were included in the statistical analysis. It should also be emphasized that in a few mice, the probe was located outside the NAcc, and in these mice, no effect of amphetamine/cocaine on accumbal dopamine release was observed (Fig. 3). It should be emphasized that in a few mice, the probe was located outside the NAcc shell, and in these mice, no effect of amphetamine or cocaine on accumbal dopamine release was observed (data not shown). Given that only amphetamine and cocaine increase accumbal dopamine compared to vehicle, it appears less likely that the probes causes structural defects within the NAcc that may influence the possibility to detect dopamine release.Fig. 3

Bottom Line: As the target circuits for ghrelin in the brain include a mesolimbic reward pathway that is intimately associated with reward-seeking behaviour, we sought to determine whether the central ghrelin signaling system is required for reward from drugs of abuse other than alcohol, namely cocaine or amphetamine.We found that amphetamine-as well as cocaine-induced locomotor stimulation and accumbal dopamine release were reduced in mice treated with a GHS-R1A antagonist.Our data suggest that the central ghrelin signaling system constitutes a novel potential target for treatment of addictive behaviours such as drug dependence.

View Article: PubMed Central - PubMed

Affiliation: Section for Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, SE-405 30, Gothenburg, Sweden. elisabet.jerlhag@pharm.gu.se

ABSTRACT

Introduction: Recently we demonstrated that genetic or pharmacological suppression of the central ghrelin signaling system, involving the growth hormone secretagogue receptor 1A (GHS-R1A), lead to a reduced reward profile from alcohol. As the target circuits for ghrelin in the brain include a mesolimbic reward pathway that is intimately associated with reward-seeking behaviour, we sought to determine whether the central ghrelin signaling system is required for reward from drugs of abuse other than alcohol, namely cocaine or amphetamine.

Results: We found that amphetamine-as well as cocaine-induced locomotor stimulation and accumbal dopamine release were reduced in mice treated with a GHS-R1A antagonist. Moreover, the ability of these drugs to condition a place preference was also attenuated by the GHS-R1A antagonist.

Conclusions: Thus GHS-R1A appears to be required not only for alcohol-induced reward, but also for reward induced by psychostimulant drugs. Our data suggest that the central ghrelin signaling system constitutes a novel potential target for treatment of addictive behaviours such as drug dependence.

Show MeSH
Related in: MedlinePlus