The Modulatory Role of Orexin 1 Receptor in Nucleus Accumbens (NAc) on Spatial Memory in Rats.

Neuropeptide orexin mainly exists in neurons within and around the lateral hypothalamus and exhibits high affinity to orexin 1 and 2 receptors (OX1R and OX2R, respectively). Orexinergic neurons send their axons to the nucleus accumbens (NAc), which expresses OX1Rs. Previous studies have shown the involvement of orexins and their role in learning and memory processes in the dorsal raphe nucleus and hippocampus. However, no study has examined the effects of orexins in the NAc on memory. The present study examined the effect of the post-training and pre-probe trial intra-NAc administration of SB-33486-A (OX1R antagonist, 12 µg/0.5µl) and TCS-OX2-29 (OX2R antagonist, 10 µg/0.5 µl) on the consolidation and retrieval of memory in the Morris Water Maze (MWM) task. In experiment 1, rats were trained in the MWM and, immediately after every training, received bilateral injections of dimethyl sulfoxide (DMSO) (control group), SB-334867-A (SB), and TCS-OX2-29 (TCS) into the NAc. Experiment 2 was similar to experiment 1, except that the rats received DMSO, SB, and TCS 15 min before the probe test. Probe and visible tests were performed after the last training, and the distance moved, escape latency, and velocity were recorded. In experiment 3, rats trained in experiments 1 and 2, immediately after the probe test, were given the trials for visuomotor coordination assessment on the visible platform. According to the results, the injection of SB increased the distance moved and escape latency in the treated groups, compared to the control group, in the consolidation phase of spatial memory (P<0.05) but not in its retrieval phase (P>0.05). However, TCS-OX2-29 had no effect. These results suggest that the inactivation of the NAc OX1Rs, but not OX2Rs, impairs the consolidation but not the retrieval of spatial memory in rats.

Role of Dopaminergic and Cannabinoidergic Receptors on Ghrelin-Induced Hypophagia in 5-Day-Old Broiler Chicken.

The present study aimed to identify the role of dopaminergic and cannabinoidergic systems in the ghrelin-induced hypophagia among meat-type chickens. In the first experiment, intracerebroventricular (ICV) injection was applied to birds with control solution, D1 receptor antagonist (5 nmol), ghrelin (6 nmol), and D1 receptor antagonist plus ghrelin. The second to sixth experiments were similar to the first one, with the difference that D2 receptor antagonist (5 nmol), D3 receptor antagonist (6.4 nmol), D4 receptor antagonist (6 nmol), the precursor of dopamine (125 nmol), and 6-hydroxy dopamine (150 nmol) instead of D1 antagonist were injected into the broiler chickens. In experiment 7, control solution and different levels of ghrelin antagonists (5, 10, and 20 nmol) were injected. In experiment 8, the chickens were ICV injected with control solution, ghrelin antagonist (10 nmol), dopamine (40 nmol), and ghrelin antagonist plus dopamine. In experiments 9 and 10, CB1 and CB2 receptors antagonist (6.25µg and 5µg) were co-injected with ghrelin (6 nmol), respectively, measuring the food intake for 120 min after the injection. It was observed that ghrelin ICV injection considerably reduced food intake, whereas ghrelin antagonist increased food intake, depending on the dose (P<0.05). In addition, ghrelin-induced hypophagia was significantly attenuated by D1 receptor antagonist and 6-hydroxy dopamine (P<0.05), while the dopamine precursor considerably elevated the ghrelin-induced food intake (P<0.05). The dopamine-induced feeding behavior was diminished by the co-administration of [D-Lys-3]-GHRP-6 (10 nmol)+dopamine (40 nmol) (P<0.05). In addition, CB1 receptor antagonists enhanced the ghrelin influence on food intake (P<0.05). The results implied that the hypophagic impact of ghrelin was probably mediated by D1 and CB1 receptors within neonatal broilers.

Consequence of dopamine D2 receptor blockade on the hyperphagic effect induced by cannabinoid CB1 and CB2 receptors in layers.

1. Endocannabinoids (ECBs) and their receptors play a regulatory function on several physiological processes such as feed-intake behaviour, mainly in the brain. This study was carried out in order to investigate the effects of the dopaminergic D1 and D2 receptors on CB1/CB2 ECB receptor-induced hyperphagia in 3-h feed-deprived neonatal layer chickens. 2. A total of 8 experiments were designed to explore the interplay of these two modulatory systems on feed intake in neonatal chickens. In Experiment 1, chickens were intracerebroventricular (ICV) injected with control solution, l-DOPA (levo-dihydroxyphenylalanine as precursor of dopamine; 125 nmol), 2-AG (2-arachidonoylglycerol as CB1 receptor agonist; 2 µg) and co-administration of l-DOPA (125 nmol) plus 2-AG (2 µg). Experiments 2-4 were similar to Experiment 1 except birds were injected with either 6-OHDA (6-hydroxydopamine as dopamine synthesis inhibitor; 150 nmol), SCH23390 (D1 receptor antagonist; 5 nmol) and AMI-193 (D2 receptor antagonist; 5 nmol) instead of l-DOPA, respectively. Additionally, Experiments 5-8 followed the previous ones using the same dose of l-DOPA, 6-OHDA and dopamine antagonists except that birds were injected with CB65 (CB2 receptor agonist; 5 µg) instead of 2-AG. Coadministrations were at the same dose for each experiment. Cumulative feed intakes were measured until 120 min after each injection. 3. ICV administration of 6-OHDA and AMI-193 significantly attenuated 2-AG-induced hyperphagia. Interestingly, the hyperphagic effect of CB65 was significantly attenuated by administration of l-DOPA, whereas the administration of 6-OHDA and AMI-193 together amplified the hyperphagic effect of CB65. 4. It was concluded that cannabinoid-induced feeding behaviour is probably modulated by dopamine receptors in neonatal layer-type chickens. It seems that their interaction may be mediated by the D2-dopamine receptor.

Differential contribution of orexin receptors within the ventral tegmental area to modulation of persistent inflammatory pain.

BACKGROUND: Orexinergic neurons in the lateral hypothalamus (LH) play an important role in pain modulation. In addition, ventral tegmental area (VTA) is known as a part of descending pain modulatory circuitry. Little is known about the interaction between the LH and neural substrates involving in modulation of formalin-induced nociception. Accordingly, we aimed to examine the pain modulatory role of VTA orexin receptors in the formalin test. METHODS: Seventy-eight male Wistar rats were unilaterally implanted with two cannulae above the LH and VTA. Intra-VTA administration of SB-334867 (orexin-1 receptor antagonist) or TCS OX2 29 (orexin-2 receptor antagonist) was performed 5 min before intra-LH microinjection of carbachol (a cholinergic receptor agonist). The procedure was followed by subcutaneous injection of formalin after 5-min interval time. RESULTS: Carbachol attenuated formalin-induced biphasic pain responses and SB-334867 or TCS OX2 29 administration dose-dependently antagonized the LH-induced analgesia during both phases. Blockade of orexin-1 and -2 receptors had more profound effects on the reduction of antinociception during the late phase compared to the early phase. Also, contribution of orexin-1 receptors in mediation of LH-induced analgesia was greater than orexin-2 receptors during the late phase. CONCLUSION: Formalin test, a model of persistent inflammatory pain, mimics the conditions encountered in clinical situations. Pain modulatory role of orexinergic system in the formalin test through a neural pathway from the LH to the VTA provides the evidence that orexins can be useful therapeutic targets for chronic pain treatment. WHAT DOES THIS STUDY ADD?: There is a pathway from the lateral hypothalamus (LH) to the ventral tegmental area (VTA) which modulates biphasic formalin-induced pain. Blockade of VTA orexin receptors dose-dependently reduces LH-induced analgesia during both phases. Anti-analgesic effect of orexin receptor antagonists is more considerable during the late phase. Contribution of orexin-1 receptors to mediation of LH-induced analgesia is more than orexin-2 receptors during the late phase.

Endocannabinoid and nitric oxide interaction mediates food intake in neonatal chicken.

The aim of the current study was to investigate the interaction of the nitric oxide and cannabinoidergic systems on feeding behaviour in neonatal chicken. A total of 6 experiments were designed to evaluate the interaction between cannabinoidergic and nitrergic systems on food intake in 3-h food-deprived (FD3) neonatal chickens. In Experiment 1, chickens received intracerebroventricular (ICV) injections of saline, 2-arachidonoylglycerol (2-AG) (a CB1 receptor agonist, 2 µg), l-arginine (nitric oxide precursor, 200 nmol) and co-administration of 2-AG + l-arginine. In Experiment 2, ICV injection of saline, 2-AG (2 µg), l-NAME (a nitric oxide synthesis inhibitor, 100 nmol) and their combination (2-AG + l-NAME) were applied to the birds. In Experiment 3, injections were saline, CB65 (a CB2 receptor agonist, 1.25 µg), l-arginine (200 nmol) and CB65 + l-arginine. In Experiment 4, birds received ICV injection of saline, CB65 (1.25 µg), l-NAME (100 nmol) and CB65 + l-NAME. In Experiment 5, chickens were ICV injected with saline, l-arginine (800 nmol), SR141716A (a selective CB1 receptor antagonist, 6.25 µg) and l-arginine + SR141716A. In Experiment 6, birds were injected with saline, l-arginine (800 nmol), AM630 (a selective CB2 receptor antagonist, 5 µg) and l-arginine + AM630. Cumulative food intake was recorded until 2-h post injection. ICV injection of CB1 and CB2 receptor agonists increased food intake. Co-injection of 2-AG + l-NAME increased the hyperphagic effects of CB1 receptors. CB2 receptor-induced food intake was not affected by co-administration of CB65 + l-NAME. l-Arginine decreased food intake and this effect was amplified by co-injection of l-arginine + SR141716A. However; CB2 receptor antagonists had no effect on l-arginine-induced hypophagia. The results suggest that there is an interaction between endogenous nitric oxide and the cannabinoidergic system on feeding behaviour which is mediated via CB1 receptors in the neonatal chicken.

5-HT(1A) receptor activation improves anti-cataleptic effects of levodopa in 6-hydroxydopamine-lesioned rats.

BACKGROUND AND THE PURPOSE OF THE STUDY: In Parkinson>s disease (PD) prolong use of L-DOPA causes some motor disorders such as wearing-off and L-DOPA induced dyskinesia (LID). In this investigation the effect of 8-OHDAPT, as a 5-HT(1A) agonist on anti-cataleptic effect of L-DOPA in 6-hydroxydopamine (6-OHDA) lesioned male Wistar rats was investigated. METHODS: Catalepsy was induced by unilateral injection of 6-OHDA (8 µg/2µl/rat) into the central region of the SNc. After 3 weeks as a recovery period, animals received intraperitoneally (i.p.) L-DOPA (15 mg/kg) twice daily for 20 days, and anti-cataleptic effect of L-DOPA was assessed by bar-test at days of 5, 10, 15 and 20. RESULTS AND MAJOR CONCLUSION: The results showed that L-DOPA had anti-cataleptic effect only until the day of 15, and its effect was decreased on the day of 20. On the day of 21, rats were co-injected with three different doses of 8-OHDAPT (0.1, 0.5 and 2.5 mg/kg, i.p.) and L-DOPA (15 mg/kg, ip). 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OHDAPT) improved anti-cataleptic effect of L-DOPA at the dose of 0.5 mg/kg. Moreover the effect of 8-OHDAPT on anti-cataleptic effect of L-DOPA (15 mg/kg, ip) was abolished by 1-(2-methyoxyphenyl)-4-[4-(2-phthalamido) butyl] piperazine hydrobromide (NAN-190; 0.5 mg/kg, i.p.) as a 5-HT(1A) receptor antagonist. According to the obtained results, it may be concluded that activation of 5-HT(1A) receptors by 8-OHDAPT may improve anti-cataleptic effect of L-DOPA in a 6-OHDA- induced rat model of PD. Further studies are required to clarify the exact mechanism of interaction between 5-HT(1A) and dopaminergic neurons.

GABAergic control of food intake in the meat-type chickens.

This study examined the effects of intracerebroventricular injections of gamma-aminobutyric acid (GABA) agonists on short-term food intake in meat-type cockerels. In Experiment 1, birds were injected with various doses of muscimol, a GABA(A) agonist. In Experiment 2, the birds received bicuculline, a GABA(A) antagonist, prior to injection of muscimol. In Experiment 3, the effect of varying doses of baclofen, a GABA(B) agonist, on food intake was determined. The intracerebroventricular injection of muscimol caused a dose-dependent increase in food intake. This effect was significantly attenuated by pretreatment with bicuculline. Food intake was not affected by the intracerebroventricular injection of baclofen. These results suggest that GABA acts within the brain of broilers at a GABA(A), but not GABA(B), receptor to increase voluntary food intake.