neuropeptide-y and 4-iodo-2-5-dimethoxyphenylisopropylamine

The feeding effects of 5-hydroxytryptamine (5-HT)(1) and 5-HT(2) receptor agonists injected into the hypothalamic paraventricular nucleus (PVN) immediately prior to PVN administration of neuropeptide Y (NPY) were examined. The impact of these same compounds on NPY-induced alterations in energy metabolism was also assessed in an attempt to characterize further the potential interactive relationship of PVN NPY and 5-HT on feeding and whole body calorimetry. Specifically, several experiments examined the effect of various 5-HT receptor agonists on NPY-stimulated eating and alterations in energy substrate utilization [respiratory quotient (RQ)]. This included the 5-HT(1A) receptor agonist 8-OH-DPAT, the 5-HT(1B/1A) agonist RU 24969, the 5-HT(1D) agonist L-694,247, the 5-HT(2A/2C) agonist DOI, the 5-HT(2B) agonist BW 723C86 and the 5-HT(2C) agonist mCPP. In feeding tests conducted at the onset of the dark cycle, drugs were administered 5 min prior to PVN injection of NPY and food intake was measured 2 h postinjection. The metabolic effects of NPY following a similar pretreatment were monitored using an open-circuit calorimeter measuring the volume of oxygen consumed (VO(2)), carbon dioxide produced (VCO(2)) and RQ (VCO(2)/VO(2)). PVN injection of NPY (100 pmol) potentiated feeding and evoked reliable increases in RQ. Only DOI (2.5--5 nmol) pretreatment antagonized NPY-induced eating and blocked the peptide's effect on energy substrate utilization. Direct PVN pretreatment with spiperone (SPRN), a 5-HT(2A) receptor antagonist, and ketanserin (KTSN), a 5-HT(2A/2C) antagonist, but not SDZ SER 082, a 5-HT(2B/2C) antagonist, or the 5-HT(2C) antagonist RS 102221, blocked the effect of DOI in both feeding and metabolic tests providing additional evidence that activation of PVN 5-HT(2A) receptors inhibits NPY's action on feeding and substrate utilization.

Topics: Amphetamines; Animals; Eating; Energy Metabolism; Male; Neuropeptide Y; Oxygen Consumption; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin; Receptors, Serotonin, 5-HT1; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Stimulation, Chemical

Bath application of alpha-melanocyte stimulating hormone (alpha-MSH) to rat hypothalamic slices inhibited the spontaneous firing rate of continuously firing neurons in the ventromedial hypothalamic nucleus or paraventricular nucleus. This inhibitory effect is most likely direct and independent of synaptic transmission. The alpha-MSH-responsive neurons tested did not respond to neuropeptide Y (NPY) application. On the other hand, alpha-MSH did not inhibit the intraburst firing rate of phasic bursting neurons, although these bursting neurons were highly responsive to a serotonin 5HT2a/2b/2c agonist with a change of firing pattern to continuous firing and an increase in firing rate which was reversed by NPY. These results suggest that a change of neuronal firing rate may represent a neural correlate of satiety induced by anorexic agents.

Topics: Action Potentials; alpha-MSH; Amphetamines; Animals; Animals, Newborn; Feeding Behavior; Hippocampus; Hypothalamus; Neurons; Neuropeptide Y; Organ Culture Techniques; Rats; Rats, Sprague-Dawley; Serotonin Receptor Agonists; Synapses; Time Factors

Hypothalamic neuropeptide Y (NPY) and serotonin (5-HT)-containing neurons are believed to exert an interactive effect on ingestive behavior. The present study examined the ability of two serotonergic antagonists, spiperone (SPIP), a 5-HT2A antagonist, and mianserin (MIAN), a 5-HT(2A/2C) antagonist, to block the inhibitory action of the 5-HT(2A/2C) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on NPY-stimulated eating. Drugs were injected directly into the paraventricular nucleus (PVN), the perifornical (PFH) or the ventromedial hypothalamus (VMH) at the onset of the dark cycle. PVN, PFH and VMH injections of NPY potentiated food intake although only PVN pretreatment with DOI (5-20 nmol) suppressed NPY-induced eating. SPIP or MIAN, injected immediately prior to PVN DOI, reversed the suppressive effect of DOI on NPY feeding. These findings are consistent with other recent data showing that 5-HT2A receptors within the PVN modulate NPY's effect on food intake at the start of the nocturnal period.

Topics: Amphetamines; Animals; Appetite Stimulants; Eating; Male; Mianserin; Neuropeptide Y; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Spiperone; Ventromedial Hypothalamic Nucleus

The present study was aimed at comparing the effects of serotonin (5-HT) synthesis blockade using chronic administration of p-chlorophenylalanine (PCPA) and 5,7-dihydroxytryptamine injections of variable volume (3 vs. 6 microl) on the density of NPY immunoreactive (Ir) neurons and binding of [3H]8-OH-DPAT, S-CM-G[125I]TNH2 and [125I]DOI to 5-HT1A, 5-HT1B/1D, and 5-HT2A/2C receptors in rat cortical regions. Three weeks after large but partial (89% depletion in 5-HT tissue concentration) lesions of 5-HT neurons no changes in neither NPY immunoreactivity nor 5-HT receptor binding were detected. The complete 5,7-DHT lesions produced increases in the number of NPY-Ir neurons in the upper regions of the cingular (134%), frontal (140%) and parietal cortex (48%) and corresponding decreases in 5-HT2A/2C binding (16-26%). No changes in 5-HT1A and 5-HT1B/1D binding were observed after lesions of this kind. After PCPA treatment, decreases in NPY-Ir neurons density (22-40%) and increases in 5-HT1A and 5-HT1B/1D receptor binding sites (20-50%) were distributed in both upper and deeper cortical regions. The lack of effect of the partial lesion suggests that spared 5-HT neurons may exert compensatory mechanisms up to a large extent. The changes in NPY immunoreactivity and 5-HT2A/2C binding detected in the upper regions of the cortex after complete 5-HT lesions probably result from local cellular rearrangements, whereas blocking 5-HT synthesis has more widespread influence on NPY neurons and on 5-HT1A and 5-HT1B/1D receptor subtypes. Moreover, decreases in DOPAC concentrations detected only after complete lesions suggest that the involvement of catecholaminergic transmission may also differentiate 5,7-DHT and PCPA treatments. Altogether, these data suggest that different receptor subtypes might be involved in 5-HT-NPY relationships.

Topics: 3,4-Dihydroxyphenylacetic Acid; 5,7-Dihydroxytryptamine; 8-Hydroxy-2-(di-n-propylamino)tetralin; Amphetamines; Animals; Binding, Competitive; Cerebral Cortex; Dipeptides; Dopamine; Female; Fenclonine; Iodine Radioisotopes; Neuronal Plasticity; Neuropeptide Y; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT1D; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin; Receptors, Serotonin, 5-HT1; Serotonin; Serotonin Agents; Tritium

The present study examined the impact of the 5-HT(2A/2C) agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on the feeding-stimulant action of neuropeptide Y (NPY) injected into three hypothalamic sites, the paraventricular nucleus (PVN), the perifornical hypothalamus (PFH) and the ventromedial nucleus (VMH). Injections of NPY (100-200 pmol) into each region potentiated food intake. Pretreatment with DOI (5-20 nmol) into the PVN effectively suppressed feeding elicited by PVN NPY (100 pmol). In contrast, DOI injections into the PFH and VMH failed to modify NPY-stimulated eating. This suggests that 5-HT(2A/2C) receptor modulation of NPY feeding within the hypothalamus is localized to the PVN.

Topics: Amphetamines; Animals; Feeding Behavior; Hypothalamic Area, Lateral; Male; Microinjections; Neuropeptide Y; Paraventricular Hypothalamic Nucleus; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin; Serotonin Receptor Agonists; Ventromedial Hypothalamic Nucleus

The effect of 5-HT1 and 5-HT2 receptor agonists administered into the paraventricular hypothalamus was studied on the hyperphagia caused by neuropeptide Y (NPY) injected into the same area. The 5-HT2A/2C receptor agonist DOI (10-20 nmol/0.5 microliter) significantly reduced NPY overeating while the 5-HT1A/1B receptor agonist RU 24969 (3.5-14 nmol/0.5 microliter) and the 5-HT1B/2C receptor agonist mCPP (5-20 nmol/0.5 microliter) had no such effect. The 5-HT2A receptor antagonist spiperone (5 microgram/0.5 microliter) and the corticotropin releasing factor antagonist alpha-helical-CRF9-41 (0.5-1 micrograms/0.5 microliter) completely antagonized the effect of 10 nmol DOI.

Topics: Amphetamines; Animals; Corticotropin-Releasing Hormone; Feeding Behavior; Hyperphagia; Indoles; Male; Neuropeptide Y; Paraventricular Hypothalamic Nucleus; Piperazines; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin; Serotonin Receptor Agonists; Spiperone