The mechanisms governing food intake and appetite regulation in the brain are intricate and vary across different animal species. Dopamine and cholecystokinin (CCK) are recognized as two critical neurotransmitters involved in the control of food intake; however, the potential interactions between these neurotransmitters remain poorly understood. Consequently, this study aimed to investigate the interactions between central CCK and the dopaminergic system in the feeding behavior of layer-type chickens. In this experiment, birds were administered intracerebroventricular (ICV) injections of CCK4, CCK8, and CCK8s at doses of 0.25, 0.5, and 1 nmol, respectively. Additionally, various compounds were injected ICV, including L-DOPA (a dopamine precursor), 6-OHDA (a dopamine synthesis inhibitor), SCH 23390 (a D1 receptor antagonist), AMI-193 (a D2 receptor antagonist), NGB 2904 (a D3 receptor antagonist), and L-741,742 (a D4 receptor antagonist), either alone or in combination with CCK8s (1 nmol). The cumulative feed consumption was measured at 30, 60, and 120 minutes following the injections. The results indicated that ICV administration of CCK4 and CCK8 did not significantly influence feeding behavior (P ≥ 0.05). In contrast, CCK8s at a dose of 1 nmol resulted in a dose-dependent reduction in feed consumption (P < 0.05). Furthermore, SCH 23390 (5 nmol) and 6-OHDA (150 nmol) mitigated the inhibitory effect of CCK8s on feed consumption (P < 0.05), whereas NGB2904 (6.4 nmol), AMI-193 (5 nmol), and L-741,742 (6 nmol) did not exhibit significant effects (P ≥ 0.05). This study substantiates the involvement of D1 receptors in the hypophagic response induced by CCK8s in layer-type chickens.

2025-01-01·EUROPEAN JOURNAL OF PHARMACOLOGY

Interaction between the dopaminergic and endocannabinoid systems promotes peripheral antinociception

Article

作者: Cristina de Sousa Fonseca, Flávia ; Lima Romero, Thiago Roberto ; Pinto Barra, Walace Cassio ; Irie, Audrey Lopes ; Gama Duarte, Igor Dimitri ; Gonçalves de Queiroz, Bárbara Formiga ; de Castro Perez, Andrea ; Viana, Giovanna Bauer

BACKGROUND:

Dopamine has been widely related to pain modulation, at central and peripheral levels. In this study we aimed to investigate the mechanisms involved in peripheral antinociception, evaluating the interaction between the dopaminergic and endocannabinoid systems in this event.

METHODS:

Male Swiss mice (30-40 g) were pre-sensitized by administration of the hyperalgesic PGE₂ (2 μg/paw). The nociceptive threshold was measured using the paw withdrawal test.

RESULTS:

Dopamine (80 ng/paw) promoted antinociception. This effect was reversed by the CB₁ and CB₂ cannabinoid receptor antagonists AM251 (20, 40, and 80 μg/paw) and AM630 (25, 50, and 100 μg/paw). JZL (4 μg/paw), an inhibitor of the degradation of the 2-arachidonylglycerol (2-AG), potentiated the antinociceptive action of the submaximal dose of dopamine (5 ng/paw). While anandamide degradation and reuptake inhibitors (MAFP 0.5 μg/paw and VDM11 2.5 μg/paw) did not promote changes in intermediate antinociception induced by dopamine. Anandamide at a submaximal dose (12.5 ng/paw) promoted intermediate antinociception that was not potentiated by the administration of the dopamine reuptake inhibitor GBR 12783 (16 μg/paw). In contrast, the administration of GBR potentiated the intermediate antinociception induced by a submaximal dose of 2-AG (10 μg/paw). Furthermore, the dopaminergic receptor antagonists D₂ Remoxipride (4 μg/paw) and D₃ U99194 (16 μg/paw) reversed the antinociception mediated by the maximum dose of this endocannabinoid (20 μg/paw). In contrast, the D₄ receptor antagonist L-745,870 (16 μg/paw) did not change the nociceptive threshold.

CONCLUSIONS:

In this way, we demonstrate the interaction between the dopaminergic and endocannabinoid systems to promote analgesia peripherally.

2024-12-01·BRAIN RESEARCH BULLETIN

Dopamine D4 receptors in the lateral habenula regulate anxiety-related behaviors in a rat model of Parkinson's disease

Article

作者: Du, Chengxue ; Li, Xiaobo ; Wang, Jiachen ; Sun, Baihua ; Chang, Mingze ; Tan, Huihui ; Han, Nannan ; Zhang, Gejuan

Although the output of the lateral habenula (LHb) controls the activity of midbrain dopamine (DA) and 5-hydroxytryptamine (5-HT) containing systems, which are implicated in the pathophysiology of anxiety, it is not clear how activation and blockade of LHb D₄ receptors affects anxiety-like behaviors, particularly in Parkinson's disease related anxiety. In this study, unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc) in rats induced anxiety-like behaviors, which attribute to hyperactivity of LHb neurons and decrease in the level of DA in the medial prefrontal cortex (mPFC), amygdala and ventral hippocampus (vHip) compared to sham-operated rats. Intra-LHb injection of D₄ receptor agonist A412997 induced or increased the expression of anxiety-like behaviors, while injection of D₄ receptor antagonist L741742 showed anxiolytic effects in sham-operated and the SNc-lesioned rats. However, the doses producing behavioral effects in the lesioned rats were higher than those of sham-operated rats. Intra-LHb injection of A412997 increased firing rate of LHb neurons, and decreased levels of DA and 5-HT in the mPFC, amygdala and vHip; conversely, L741742 decreased firing rate of LHb neurons, and increased levels of DA and 5-HT in two groups of rats. Compared to sham-operated rats, the duration of A412997 and L741742 action on the firing rate of neurons was markedly shortened in the lesioned rats. Collectively, these findings suggest that D₄ receptors in the LHb are involved in the regulation of anxiety-like behaviors, and degeneration of the nigrostriatal pathway down-regulates function and/or expression of these receptors.

100 项与 D4 receptor antagonists(University of Bari) 相关的药物交易

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