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CB1 cannabinoid receptors are involved in neuroleptic-induced enhancement of brain neurotensin.

Hassanzadeh P, Rostami F - Iran J Basic Med Sci (2014)

Bottom Line: Chronic, but not acute, treatment with the highest dose of fluphenazine or amisulpride resulted in significant enhancement of neurotensin contents in the prefronatal cortex and nucleus accumbens.AM251 showed no effect by itself.The brain neurotensin under the regulatory action of CB1 receptors is involved in  the effects of amisulpride and fluphenazine.

View Article: PubMed Central - PubMed

Affiliation: Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran.

ABSTRACT

Unlabelled: Objective(s ): Targeting the neuropeptide systems has been shown to be useful for the development of more effective antipsychotic drugs. Neurotensin, an endogenous neuropeptide, appears to be involved in the mechanism of action of antipsychotics. However, the available data provide conflicting results and the mechanism(s) by which antipsychotics affect brain neurotensin neurotransmission have not been identified. Therefore, we aimed to investigate the effects of fluphenazine and amisulpride on brain regional contents of neurotensin considering the role of cannabinoid CB1 receptors which interact with neurotensin neurotransmission.

Materials and methods: Fluphenazine (0.5, 1, and 3 mg/kg) or amisulpride (3, 5, and 10 mg/kg) were administered intraperitoneally to male Wistar rats either for one day or 28 consecutive days. Twenty four hours after the last injection of drug or vehicle, neurotensin contents were determined in the mesocorticolimbic and nigrostriatal dopamine regions by radioimmunoassay. In the case of any significant change, the effect of pre-treatment with CB1 receptor antagonist, AM251 was investigated.

Results: Chronic, but not acute, treatment with the highest dose of fluphenazine or amisulpride resulted in significant enhancement of neurotensin contents in the prefronatal cortex and nucleus accumbens. Fluphenazine also elevated neurotensin levels in the anterior and posterior caudate nuclei and substantia nigra. Neither amisulpride nor fluphenazine affected neurotensin contents in the amygdala or hippocampus. Pre-treatment with AM251 (3 mg/kg) prevented the neuroleptic-induced elevation of neurotensin. AM251 showed no effect by itself.

Conclusion: The brain neurotensin under the regulatory action of CB1 receptors is involved in  the effects of amisulpride and fluphenazine.

No MeSH data available.


Related in: MedlinePlus

AM251 alone does not affect brain regional levels of neurotensin. A: Single injection of 3 mg/kg AM251, B: 28-day treatment with 3 mg/kg AM251. Data represent means ± SEM of n=6/group
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Figure 4: AM251 alone does not affect brain regional levels of neurotensin. A: Single injection of 3 mg/kg AM251, B: 28-day treatment with 3 mg/kg AM251. Data represent means ± SEM of n=6/group

Mentions: Acute or 28-day treatment with AM251 (3 mg/kg) alone did not alter neurotensin content in any brain region analyzed (Figure 4A and B, P>0.05).


CB1 cannabinoid receptors are involved in neuroleptic-induced enhancement of brain neurotensin.

Hassanzadeh P, Rostami F - Iran J Basic Med Sci (2014)

AM251 alone does not affect brain regional levels of neurotensin. A: Single injection of 3 mg/kg AM251, B: 28-day treatment with 3 mg/kg AM251. Data represent means ± SEM of n=6/group
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4016688&req=5

Figure 4: AM251 alone does not affect brain regional levels of neurotensin. A: Single injection of 3 mg/kg AM251, B: 28-day treatment with 3 mg/kg AM251. Data represent means ± SEM of n=6/group
Mentions: Acute or 28-day treatment with AM251 (3 mg/kg) alone did not alter neurotensin content in any brain region analyzed (Figure 4A and B, P>0.05).

Bottom Line: Chronic, but not acute, treatment with the highest dose of fluphenazine or amisulpride resulted in significant enhancement of neurotensin contents in the prefronatal cortex and nucleus accumbens.AM251 showed no effect by itself.The brain neurotensin under the regulatory action of CB1 receptors is involved in  the effects of amisulpride and fluphenazine.

View Article: PubMed Central - PubMed

Affiliation: Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran.

ABSTRACT

Unlabelled: Objective(s ): Targeting the neuropeptide systems has been shown to be useful for the development of more effective antipsychotic drugs. Neurotensin, an endogenous neuropeptide, appears to be involved in the mechanism of action of antipsychotics. However, the available data provide conflicting results and the mechanism(s) by which antipsychotics affect brain neurotensin neurotransmission have not been identified. Therefore, we aimed to investigate the effects of fluphenazine and amisulpride on brain regional contents of neurotensin considering the role of cannabinoid CB1 receptors which interact with neurotensin neurotransmission.

Materials and methods: Fluphenazine (0.5, 1, and 3 mg/kg) or amisulpride (3, 5, and 10 mg/kg) were administered intraperitoneally to male Wistar rats either for one day or 28 consecutive days. Twenty four hours after the last injection of drug or vehicle, neurotensin contents were determined in the mesocorticolimbic and nigrostriatal dopamine regions by radioimmunoassay. In the case of any significant change, the effect of pre-treatment with CB1 receptor antagonist, AM251 was investigated.

Results: Chronic, but not acute, treatment with the highest dose of fluphenazine or amisulpride resulted in significant enhancement of neurotensin contents in the prefronatal cortex and nucleus accumbens. Fluphenazine also elevated neurotensin levels in the anterior and posterior caudate nuclei and substantia nigra. Neither amisulpride nor fluphenazine affected neurotensin contents in the amygdala or hippocampus. Pre-treatment with AM251 (3 mg/kg) prevented the neuroleptic-induced elevation of neurotensin. AM251 showed no effect by itself.

Conclusion: The brain neurotensin under the regulatory action of CB1 receptors is involved in  the effects of amisulpride and fluphenazine.

No MeSH data available.


Related in: MedlinePlus