Decreased taste sensitivity to sucrose in dopamine D3 receptor mutant mice.

Dopamine plays a key role in food rewards and sweet-taste stimulation. We examined the basis for behavioral responses to sweet taste in dopamine D3 receptor-deficient (D3-/-) mice by determining whether the absence of D3 receptors affects the sensitivity to dilute sucrose solutions. In experiment 1, we measured the intensity generalization threshold of conditioned taste aversion (CTA) to a 0.2 M sucrose solution. Results showed that the generalization thresholds were 0.025-0.05 M in D3-/- mice and 0.0025-0.005 M in wild-type (WT) mice. In experiment 2, we found that D3-/- and WT mice had similar capabilities to form and extinguish CTAs. Since the intensity generalization threshold is mainly due to a combination of sweet-taste sensitivity and the robust nature of CTA formation, the results showed that taste sensitivity to sucrose in D3-/- mice was lower than that in WT mice. In experiment 3, to test whether the peripheral sensory signaling may also be affected by the disruption of the dopamine D3 receptors, the mRNA expression levels of sweet-taste-related proteins in taste buds of D3-/- mice were determined. The T1R1 and BDNF mRNA expression levels in D3-/- mice were higher than the controls, whereas T1R2, T1R3, α-gustducin, and TRPM5 mRNA were similar. These findings suggest that disruption of dopamine D3 receptor-mediated signaling decreases the sweet-taste sensitivity and alters the mRNA expression levels of some taste-related molecules.

Taste sensitivity to sucrose is lower in outbred Sprague-Dawley phenotypic obesity-prone rats than obesity-resistant rats.

The purpose of the present study was to better understand the role of sweet taste perception in dietary behavior and body weight in outbred Sprague-Dawley phenotypic obesity-prone and obesity-resistant rats by measuring sucrose taste sensitivity using a conditioned taste aversion paradigm. Rats were given a high fat diet for 2 weeks and were assigned as obesity-prone (P, upper tertile) or obesity-resistant (R, lower tertile) based on weight gain. Each group was then given either chow (C, 10% fat) or the high fat diet (F, 46% fat) for the remainder of the experiment (∼18 weeks) such that there were four groups - obesity-prone on chow (C-P), obesity-prone on high fat (H-P), obesity-resistant on chow (C-R), obesity-resistant on high fat (H-R). The sucrose sensitivity of phenotypic obesity-prone rats is lower than that of obesity-resistant rats in either H-fed or C-fed group, and all H-fed rats were more sensitivity than their C-fed counterparts (H-P vs. C-P; H-R vs. C-R). Body weight gain and total calories intake of phenotypic obesity-prone rats are more than that of obesity-resistant rats. The results suggest that lower sucrose taste sensitivity may contribute to body weight gain and total calories intake of phenotypic obesity-prone rats compared to obesity-resistant rats, and there is correlation between the change in the sweet taste threshold and diet treatment.

Rapid Thermochromic and Highly Thermally Conductive Nanocomposite Based on Silicone Rubber for Temperature Visualization Thermal Management in Electronic Devices.

Effective heat dissipation and real-time temperature monitoring are crucial for ensuring the long-term stable operation of modern, high-performance electronic products. This study proposes a silicon rubber polydimethylsiloxane (PDMS)-based nanocomposite with a rapid thermal response and high thermal conductivity. This nanocomposite enables both rapid heat dissipation and real-time temperature monitoring for high-performance electronic products. The reported material primarily consists of a thermally conductive layer (Al2O3/PDMS composites) and a reversible thermochromic layer (organic thermochromic material, graphene oxide, and PDMS nanocoating; OTM-GO/PDMS). The thermal conductivity of OTM-GO/Al2O3/PDMS nanocomposites reached 4.14 W m-1 K-1, reflecting an increase of 2200% relative to that of pure PDMS. When the operating temperature reached 35, 45, and 65 °C, the surface of OTM-GO/Al2O3/PDMS nanocomposites turned green, yellow, and red, respectively, and the thermal response time was only 30 s. The OTM-GO/Al2O3/PDMS nanocomposites also exhibited outstanding repeatability and maintained excellent color stability over 20 repeated applications.

Lesions of mediodorsal thalamic nucleus reverse abnormal firing of the medial prefrontal cortex neurons in parkinsonian rats.

The dysfunction of the medial prefrontal cortex is associated with affective disorders and non-motor features in Parkinson's disease. However, the exact role of the mediodorsal thalamic nucleus in the function of the prefrontal cortex remains unclear. To study the possible effects of the mediodorsal thalamic nucleus on the neurological function of the medial prefrontal cortex, a model of Parkinson's disease was established by injecting 8 µg 6-hydroxydopamine into the substantia nigra compacta of rats. After 1 or 3 weeks, 0.3 µg ibotenic acid was injected into the mediodorsal thalamic nucleus of the midbrain. At 3 or 5 weeks after the initial injury, neuronal discharge in medial prefrontal cortex of rat brain was determined electrophysiologically. The numbers of dopamine-positive neurons and tyrosine hydroxylase immunoreactivity in substantia nigra compacta and ventral tegmental area were detected by immunohistochemical staining. Results demonstrated that after injury, the immunoreactivity of dopamine neurons and tyrosine hydroxylase decreased in the substantia nigra compacta and ventral tegmental areas of rats. Compared with normal medial prefrontal cortical neurons, at 3 and 5 weeks after substantia nigra compacta injury, the discharge frequency of pyramidal neurons increased and the discharge pattern of these neurons tended to be a burst-discharge, with an increased discharge interval. The discharge frequency of interneurons decreased and the discharge pattern also tended to be a burst-discharge, but the discharge interval was only higher at 3 weeks. At 3 weeks after the combined lesions, the discharge frequency, discharge pattern and discharge interval were restored to a normal level in pyramidal neurons and interneurons in medial prefrontal cortex. These findings have confirmed that mediodorsal thalamic nucleus is involved in regulating neuronal activities of the medial prefrontal cortex. The changes in the function of the mediodorsal thalamic nucleus may be associated with the abnormal discharge activity of the medial prefrontal cortex neurons after substantia nigra compacta injury. All experimental procedures were approved by the Institutional Animal Care and Use Committee of Xi'an Jiaotong University, China (approval No. XJTULAC2017-067) on August 26, 2017.

[µ-opioid receptors in the central nucleus of the amygdala mediate sodium intake in rats].

OBJECTIVE: To investigate the opioidergic mechanism of the central nucleus of the amygdala (CeA) for regulating sodium appetite in rats. METHDOS: Using the elaborate invasive cerebral cannulation and brain microinjection method, we observed the effects of bilateral intra-CeA injections of DAMGO (a selective µ-opioid receptor agonist) and CTAP (a highly selective µ-opioid receptor antagonist), either alone or in combination, on NaCl solution (0.3 mol/L) and water intake by rats in different models of Na+ ingestion. RESULTS: In the two-bottle tests, bilateral injections of DAMGO at 1, 2, and 4 nmol into the CeA induced a dose-related increase of NaCl and water intake in rats treated with water deprivation with partial rehydration (WD-PR), and pretreatment with 0.5, 1, and 2 nmol CTAP injected into the CeA significantly suppressed DAMGO-induced NaCl and water intake in a dose-dependent manner: in the one-bottle tests, bilateral injections of DAMGO (2 noml) into the CeA had no effect on water intake of the rats. In rats with subcutaneous injection of furosemide (FURO) combined with captopril (CAP) (FURO+CAP), bilateral intra-CeA injections of DAMGO (2 nmol) caused increased NaCl and water intake in the two-bottle tests, but such effects were suppressed by pretreatment with CTAP injection into the CeA; in the one-bottle tests, bilateral intra-CeA injections of DAMGO had no effect on water intake of the rats. CONCLUSION: µ-opioid receptors in the CeA are involved in the excitatory regulation of sodium appetite to mediate sodium intake. µ-opioid receptor antagonists are expected to be targets for developing inhibitors of sodium appetite.

[Effect of 5-HT7 receptor agonist on pyramidal neurons in the medial frontal cortex in a rat model of Parkinson's disease].

OBJECTIVE: To investigate the activity of pyramidal neurons in the medial prefrontal cortex (mPFC) of normal and 6-OHDA-lesioned rats and the responses of the neurons to 5-hydroxytryptamine-7 (5-HT(7)) receptor stimulation. METHODS: The changes in spontaneous firing of the pyramidal neurons in the mPFC in response to 5-HT(7) receptor stimulation were observed by extracellular recording in normal and 6-OHDA-lesioned rats. RESULTS: Both systemic and local administration of 5-HT(7) receptor agonist AS 19 resulted in 3 response patterns (excitation, inhibition and no change) of the pyramidal neurons in the mPFC of normal and 6-OHDA-lesioned rats. In normal rats, the predominant response of the pyramidal neurons to AS 19 stimulation was excitatory, and the inhibitory effect of systemically administered AS 19 was reversed by GABAA receptor antagonist picrotoxinin. In the lesioned rats, systemic administration of AS 19 also increased the mean firing rate of the pyramidal neurons, but the cumulative dose for producing excitation was higher than that in normal rats. Systemic administration of AS 19 produced an inhibitory effect in the lesioned rats, which was partially reversed by picrotoxinin. Local administration of AS 19 at the same dose did not change the ?ring rate of the neurons in the lesioned rats. CONCLUSION: The activity of mPFC pyramidal neurons is directly or indirectly regulated by 5-HT7 receptor, and degeneration of the nigrostriatal pathway leads to decreased response of these neurons to AS 19.

[µ-opioid receptors in the central nucleus of the amygdala regulate food rather than water intake in rats].

OBJECTIVE: To investigate the effect of µ-opioid receptors (µ-ORs) in the central nucleus of the amygdala (CeA) on feeding and drinking behaviors in rats and evaluate the role of glutamate signaling in opioid-mediated ingestive behaviors. METHODS: Stainless steel cannulas were implanted in the unilateral CeA for microinjection of different doses of the selective µ-OR agonist DAMGO in satiated or water-deprived male SD rats. The subsequent food intake or water intake of the rats was measured at 60, 120, and 240 min after the injection. The rats receiving microinjections of naloxone (NTX, a nonselective opioid antagonist) or D-AP-5 (a selective N-methyl-D-aspartic acid-type glutamate receptor antagonist) prior to DAMGO microinjection were tested for food intake at 60, 120, and 240 min after the injections. RESULTS: Injections of DAMGO (1-4 nmol in 0.5 µl) into the CeA significantly increased food intake in satiated rats, but did not affect water intake in rats with water deprivation. NTX (26.5 nmol in 0.5 µl) injected into the CeA antagonized DAMGO-induced feeding but D-AP-5 (6.3-25.4 nmol in 0.5 µl) injections did not produce such an effect. CONCLUSION: µ-ORs in the CeA regulate food intake rather than water intake in rats, and the orexigenic role of µ-ORs is not dependent on the activation of the NMDA receptors in the CeA.

Activation of µ-opioid receptors in the central nucleus of the amygdala induces hypertonic sodium intake.

Opioid mechanisms are involved in the control of water and NaCl intake and opioid receptors (ORs) are present in the central nucleus of the amygdala (CeA), a site of important facilitatory mechanisms related to the control of sodium appetite. Therefore, in the present study we investigated the effects of the activation of µ-ORs in the CeA on 0.3 M NaCl and water intake in rats. Male Sprague-Dawley rats with stainless steel cannulas implanted bilaterally in the CeA were used. In rats submitted to water deprivation-partial rehydration, bilateral injections of the selective µ-OR agonist [D-Ala², N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) in the doses of 1, 2, and 4 nmol into the CeA induced a dose-related increase of 0.3M NaCl intake and water intake, and bilateral injections of the selective µ-OR antagonist D-Phe-Cys-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) in the doses of 0.5, 1, and 2 nmol into the CeA produced a dose-related decrease of 0.3 M NaCl and water intake induced by DAMGO 2 nmol into the same site. In rats treated with the diuretic furosemide (10 mg/kg b.w.) combined with the angiotensin-converting enzyme inhibitor captopril (5 mg/kg b.w.) injected subcutaneously, bilateral injections of DAMGO 2 nmol into the CeA increased 0.3 M NaCl intake and water intake and the blockade of µ-ORs with CTAP 1 nmol injected into the CeA reduced the increase in 0.3 M NaCl intake and water intake induced by DAMGO 2 nmol into the same site. Bilateral injections of DAMGO into the CeA did not change urinary volume, sodium urinary excretion and mean arterial pressure, but increased activity. Thus stimulating µ-ORs in the CeA increases hypertonic sodium intake, whereas antagonizing these sites inhibits hypertonic sodium intake. Together, our results implicate µ-ORs in the CeA in a positive regulation of sodium intake.

Microinjection of NMDA-type glutamate receptor agonist NMDA and antagonist D-AP-5 into the central nucleus of the amygdale alters water intake rather than food intake.

OBJECTIVE: To investigate the role of N-Methyl-D-aspartic acid (NMDA)-type glutamate receptors in the central nucleus of the amygdale (CeA) in food and water intake. METHODS: Male Sprague-Dawley rats with stainless steel cannulae implanted unilaterally into the CeA were used. The prototypic NMDA receptor agonist NMDA, or the selective NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP-5) was microinjected into the CeA of satiated and euhydrated rats. RESULTS: Intra-CeA injection of 8.50, 17.00, or 34.00 nmol NMDA did not alter food intake but significantly increased water intake 0-1 h after the injection (F(3,32)=3.191, P=0.037) independent of food intake. Without affecting the food intake, injection of 6.34, 12.70, or 25.40 nmol D-AP-5 into the CeA significantly decreased water intake 0-1 h after the injection (F(3,28)=3.118, P=0.042) independent of food intake. CONCLUSION: NMDA receptors in the CeA may participate in the control of water intake rather than food intake.

[µ-opioid receptors in the central nucleus of the amygdala modulate sucrose solution intake in rats].

OBJECTIVE: To explore the role of µ-opioid receptors (MOR) in the central nucleus of the amygdala (CeA) in modulating sucrose solution intake in rats. METHODS: Sprague-Dawley rats received intra-CeA injection of MOR agonist DAMGO or saline, and then underwent two bottle choice test between sucrose solution and distilled water. After intake of sucrose solution or distilled water, activated neurons in the CeA were labeled and identified with MOR/Fos-double labeling immunohistochemistry. RESULTS: Compared with saline injection, intra-CeA injection of DAMGO significantly increased sucrose solution intake in rats over a 3-h period. Sucrose solution intake induced significantly more c-Fos and MOR/Fos double-labeled neurons in the CeA than distilled water intake. CONCLUSIONS: The CeA participates in modulation of sucrose intake in rats, and MOR may partly mediate this mechanism.