P2-receptor modulation of noradrenergic neurotransmission in rat kidney

1. ATP has previously been shown to act as a sympathetic cotransmitter in the rat kidney. The present study analyses the question of whether postganglionic sympathetic nerve endings in the kidney possess P2-receptors which modulate noradrenaline release. Rat kidneys were perfused with Krebs-Henseleit solution containing the noradrenaline uptake blockers cocaine and corticosterone and the alpha2-adrenoceptor antagonist rauwolscine. The renal nerves were electrically stimulated, in most experiments by 30 pulses applied at 1 Hz. The outflow of endogenous noradrenaline (or, in some experiments, of ATP and lactate dehydrogenase) as well as the perfusion pressure were measured simultaneously. 2. The P2-receptor agonist adenosine-5'-O-(3-thiotriphosphate) (ATPgammaS, 3-30 microM) reduced the renal nerve stimulation (RNS)-induced outflow of noradrenaline (estimated EC50 =8 microM). The P2-receptor antagonist cibacron blue 3GA (30 microM) shifted the concentration-inhibition curve for ATPgammaS to the right (apparent pKB value 4.7). 3. Cibacron blue 3GA (3-30 microM) and its isomer reactive blue 2 (3-30 microM) significantly increased RNS-induced outflow of noradrenaline in the presence of the P1-receptor antagonist 8-(p-sulphophenyl)theophylline (8-SPT, 100 microM) by about 70% and 90%, respectively. The P2-receptor antagonist suramin (30-300 microM) only tended to enhance RNS-induced outflow of noradrenaline. When the nerves were stimulated by short pulse trains consisting of 6 pulses applied at 100 Hz (conditions under which autoinhibition is inoperative), reactive blue 2 did not affect the RNS-induced outflow of noradrenaline. 4. RNS (120 pulses applied at 4 Hz) induced the outflow of ATP but not of the cytoplasmatic enzyme lactate dehydrogenase. 5. ATPgammaS (3-30 microM) concentration-dependently reduced pressor responses to RNS at 1 Hz. Cibacron blue 3GA, reactive blue 2 as well as suramin also reduced pressor responses to RNS (maximally by 50 to 70%). 6. This study in rat isolated kidney, in which the release of endogenous noradrenaline was measured, demonstrates that renal sympathetic nerves possess prejunctional P2-receptors that mediate inhibition of transmitter release. These prejunctional P2-receptors are activated by endogenous ligands, most likely ATP, released upon nerve activity. Both, P2-receptor agonists and P2-receptor antagonists reduced pressor responses to RNS either by inhibiting transmitter release or by blocking postjunctional vasoconstrictor P2-receptors.     

Acetyl-L-carnitine modulates glucose metabolism and stimulates glycogen synthesis in rat brain

A rapid and accurate voltammetric method for the quantitative determination of 2-mercapto-5-phenylammino-1,3,4-thiadiazole (MPATD) with carbon paste electrodes (CPE) has been developed. The study was made by cyclic voltammetry between -0.4 and +0.6 V with 50 mV s(-1) sweep rate in aqueous solution. After successive oxidation/reduction cycles we found a total oxidation of MPATD at +0.45 V. As the compound is oxidated, the reduction current peak increases at +0.13 V, indicating an irreversible process. Following only the oxidation process in the -0.1 to +0.6 V range, we investigated the optimum scan rates at different current densities and pH values (realised with buffers, pH between 1.0 and 10.0) with CPE versus Ag/AgCl reference electrode using linear sweep voltammetry. We found a good linear relation between the current peak height and concentration in a 2.5 x 10(-9)-1.25 x 10(-7) mol ml(-1). This method allows the quantitative detection of the MPATD as it or from dosage forms and biological media.     

Olfactory bulb development is altered in small-eye (Sey) mice

Small-eye (Sey) is a spontaneous, semidominant murine mutation that results from a point mutation in the Pax-6 gene. Both the eyes and the olfactory system fail to develop in homozygotes and these animals die neonatally. Heterozygotes (Sey/+) have different degrees of eye abnormalities including decreased lens size and cataracts. In the present study, we examined whether one mutated allele of Pax-6 also affects olfactory system development. By 42 days of age, main olfactory bulb volume was significantly decreased in Sey/+ animals compared with wild-type littermates, and this effect was even more dramatic in 70-day-old animals. In contrast, there was no effect on accessory olfactory bulb, olfactory epithelial, or vomeronasal organ development at any age in Sey/+ animals, demonstrating the specificity of the effect. In the main olfactory bulb, the largest differences in laminar volume were found in the glomerular and granule cell layers. These layers contain the olfactory bulb interneurons, and a subpopulation of these cells were found to be Pax-6 immunoreactive. Examination of the neurochemical consequences of this mutation showed that the number of both tyrosine hydroxylase (TH)- and gamma-aminobutyric acid (GABA)-immunoreactive profiles were dramatically decreased in Sey/+ animals as compared with controls. In contrast, neither calretinin nor calbindin immunoreactivity was affected by this mutation. Dual-labeling immunohistochemistry showed that nearly all TH-immunoreactive cells and a subpopulation of GABA-immunoreactive cells coexpressed Pax-6. However, calretinin- and calbindin-immunoreactive cells were not Pax-6 immunopositive. These data indicate that two normal alleles of Pax-6 are required for normal olfactory bulb development and, as part of this effect, this gene may be involved in the development of specific neurotransmitter systems.     

Olfactory function in young adolescents with Down's syndrome

Decreased ability to smell is present in adults with Down's syndrome, many of whom are known to have brain pathology analogous to that seen in Alzheimer's disease. Because olfactory loss is well documented in Alzheimer's disease, the question arises whether young adolescents with Down's syndrome, who have no clear Alzheimer's disease-like neuropathology, also exhibit olfactory dysfunction. To consider this issue, standardised tests of odour discrimination and identification were administered to 20 young adolescents with Down's syndrome (mean age (SD) 13.89 (1.98) years) and their test scores were compared with 20 mentally retarded and 20 non-mentally retarded control subjects matched to the patients with Down's syndrome on the basis of cognitive ability. No significant differences in olfactory function were found among the three study groups. These findings, along with those from studies of olfactory function in older patients with Down's syndrome, suggest that Down's syndrome related olfactory dysfunction occurs only at ages when Alzheimer's disease-like pathology is present.     

Neurocalcin immunoreactivity in the rat main olfactory bulb

The morphological characteristics and distribution of neurocalcin (NC)-immunoreactive elements were studied in the rat main olfactory bulb (OB) using a polyclonal antibody and the avidin-biotin immunoperoxidase method. NC-positive elements were abundant in the glomerular layer (GL), where numerous immunostained external tufted cells and periglomerular cells were detected. Other less abundant NC-immunolabeled populations included middle and internal tufted cells, Van Gehuchten cells, horizontal cells, vertical cells of Cajal, deep short-axon cells and granule cells. This study demonstrates the presence of NC immunoreactivity in subsets of different neuronal types in the rat main OB. This calcium-binding protein has been found in interneurons, and no evidence of immunoreactivity to NC is detected in projecting neurons. Despite the large population of labeled external tufted cells, most of them belong according to morphological criteria to the local circuit group and some others to those with interbulbar and/or intrabulbar connections. The identification of neuronal subpopulations expressing NC provides a further characterization and shows the existence of biochemical differences within morphologically identical neurons. Thus, this marker may be a useful tool in unravelling the circuitries of the rodent OB in both normal and experimental conditions. The exact physiological function of NC in the olfactory system remains unknown. On the basis of similarities to recoverin, it could be involved in mechanisms responsible for sensory adaptation. Additionally, its calcium-binding abilities may contribute to improve the temporal precision of stimuli transmission, or be concerned with general calcium-related events occurring in specific interneuronal groups.     

Contribution of glycogen and exogenous glucose to glucose metabolism during ischemia in the hypertrophied rat heart

Although hypertrophied hearts have increased rates of glycolysis under aerobic conditions, it is controversial as to whether glucose metabolism during ischemia is altered in the hypertrophied heart. Because endogenous glycogen stores are a key source of glucose during ischemia, we developed a protocol to label the glycogen pool in hearts with either [3H]glucose or [14C]glucose, allowing for direct measurement of both glycogen and exogenous glucose metabolism during ischemia. Cardiac hypertrophy was produced in rats by banding the abdominal aorta for an 8-week period. Isolated hearts from aortic-banded and sham-operated rats were initially perfused under substrate-free conditions to decrease glycogen content to 40% of the initial pool size. Resynthesis and radiolabeling of the glycogen pool with [3H]glucose or [14C]glucose were accomplished in working hearts by perfusion for a 60-minute period with 11 mmol/L [3H]glucose or [14C]glucose, 0.5 mmol/L lactate, 1.2 mmol/L palmitate, and 100 mumol/mL insulin. Although glycolytic rates during the aerobic perfusion were significantly greater in hypertrophied hearts compared with control hearts, glycolytic rates from exogenous glucose were not different during low-flow ischemia. The contribution of glucose from glycogen was also not different in hypertrophied hearts compared with control hearts during ischemia (1314 +/- 665 versus 776 +/- 310 nmol.min-1.g dry wt-1, respectively). Glucose oxidation rates decreased during ischemia but were not different between the two groups. However, in both hypertrophied and control hearts, the ratio of glucose oxidation to glycolysis was greater for glucose originating from glycogen than from exogenous glucose. Our data demonstrate that glycogen is a significant source of glucose during low-flow ischemia, but the data do not differ between hypertrophied and control hearts.     

Dorsal noradrenergic bundle and selective attention in the rat.

Tested the role for the dorsal noradrenergic bundle (DNB) in selective attention and stimulus filtering in 4 experiments with 138 male Wistar rats. The DNB was damaged by stereotaxically guided injection of 4 μg of the neurotoxin 6-hydroxydopamine (6-OHDA). The latent inhibition effect was blocked by 6-OHDA-induced depletion of forebrain noradrenaline, whereas nonreversal shift performance was better in noradrenaline-depleted Ss than controls. Data indicate that Ss with DNB lesions are impaired in ignoring irrelevant stimuli. In situations in which control Ss did not learn to ignore irrelevant stimuli, no lesion-induced difference was found. Thus, controls and DNB lesioned Ss learned equally about each of 2 dimensions of a multiple-redundant discrimination task. This was assessed both by interpolated trials with only 1 dimension present and by shifts in which only 1 of the previous 2 dimensions remained relevant. It is concluded that the DNB lesion does not increase stimulus sampling globally but that it impairs performance only in those cases in which normal rats learn to ignore irrelevant stimuli. (53 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute modulation of rat hepatic lipid metabolism by sulphur-substituted fatty acid analogues

A single oral dose of two 3-thia (3-thiadicarboxylic and tetradecylthioacetic acids) and of 4-thia (tetradecylthiopropionic acid) fatty acids were administered to normolipidemic rats and their effects on lipid metabolism over a 24 hr period were studied. All three thia fatty acids could be detected in plasma 2 hr after treatment. Tetradecylthioacetic and tetradecylthiopropionic acids were detected in different hepatic lipid fractions but were incorporated mainly into hepatic phospholipids. Two hours after administration hepatic mitochondrial beta-oxidation and the total liver level of long-chain fatty acyl-CoA increased with a concomitant decrease in saturated fatty acids, total hepatic malonyl-CoA and plasma triacylglycerol levels in the 3-thia fatty acid groups. Tetradecylthiopropionic acid administration caused a decrease in mitochondrial beta-oxidation and an increase in plasma triacylglycerol at 24 hr. The activities of key lipogenic enzymes were unaffected in all treatment groups. Plasma cholesterol level was reduced only at 8 hr in 3-thiadicarboxylic acid treated rats although 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase was suppressed already at 2, 4, 8 and 12 hr. The results show that thia fatty acids are rapidly absorbed and are systemically available after oral administration but the 3-thia fatty acids reached systemic circulation more slowly and less completely than the 4-thia fatty acid. Very low levels of the thia fatty acids are detected in plasma 24 hr after a single administration. They are incorporated into all hepatic lipid classes, especially phospholipids. Rapid incorporation of a non beta-oxidizable thia fatty acid into hepatic lipids may cause a diversion of other fatty acids from glycerolipid biosynthesis to mitochondrial beta-oxidation. Stimulation of mitochondrial beta-oxidation and suppression of HMG-CoA reductase are primary events, occurring within hours, after 3-thia fatty acid administration. The hypotriglyceridemic effect of the 3-thia fatty acids observed at 2-4 hr is independent of the activities of key lipogenic and triacylglycerol synthesising enzymes.     

Synaptic organization and neurotransmitters in the rat accessory olfactory bulb

The accessory olfactory bulb (AOB) is the first relay station in the vomeronasal system and may play a critical role in processing pheromone signals. The AOB shows similar but less distinct lamination compared with the main olfactory bulb (MOB). In this study, synaptic organization of the AOB was analyzed in slice preparations from adult rats by using both field potential and patch-clamp recordings. Stimulation of the vomeronasal nerve (VN) evoked field potentials that showed characteristic patterns in different layers of the AOB. Current source density (CSD) analysis of the field potentials revealed spatiotemporally separated loci of inward current (sinks) that represented sequential activation of different neuronal components: VN activity (period I), synaptic excitation of mitral cell apical dendrites (period II), and activation of granule cells by mitral cell basal dendrites (period III). Stimulation of the lateral olfactory tract also evoked field potentials in the AOB, which indicated antidromic activation of the mitral cells (period I and II) followed by activation of granule cells (period III). Whole cell patch recordings from mitral and granule cells of the AOB supported that mitral cells are excited by VN terminals and subsequently activate granule cells through dendrodendritic synapses. Both CSD analysis and patch recordings provided evidence that glutamate is the neurotransmitter at the vomeronasal receptor neuron; mitral cell synapses and both NMDA and non-NMDA receptors are involved. We also demonstrated electrophysiologically that reciprocal interaction between mitral and granule cells in the AOB is through the dendrodendritic reciprocal synapses. The neurotransmitter at the mitral-to-granule synapses is glutamate and at the granule-to-mitral synapse is gamma-aminobutyric acid. The synaptic interactions among receptor cell terminals, mitral cells, and granule cells in the AOB are therefore similar to those in the MOB, suggesting that processing of chemosensory information in the AOB shares similarities with that in the MOB.     

Olfactory bulbectomy: Neural structures involved in irritability and aggression in the male rat.

Performed bilateral ablations of the main olfactory bulbs of 12 male hooded rats (main OB group), of the main and accessory bulbs of 21 Ss (OB + AOB group), of the bulbs and areas caudal to the bulbs of 20 Ss (supra-OB group), and of the caudal areas only on 9 Ss (caudal group). Sham bulbectomy was performed on 7 Ss, and 8 controls were unoperated. The supra-OB and caudal groups became extremely irritable and the OB + AOB group somewhat irritable, while the main OB group was unchanged in irritability. Mouse killing increased within all groups. Postoperative irritability, but not killing, was highly correlated with extent of brain damage, while killing was correlated with irritability. It is concluded that bulbectomy-induced irritability is dependent upon damage to areas within and caudal to the bulbs to which the stria terminalis projects, and that both the irritability and killing are the result of altering a common motivational mechanism. (52 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Olfactory epithelium of the rat. Lectin-mediated histochemical studies

BACKGROUND: Twenty-nine patients with large bulbous and giant aneurysms of the paraclinoid segment of the internal carotid artery (ICA) were operated on, using Dolenc's combined epi- and subdural approach, between 1985 and 1994. Ages ranged from 25 to 79 (83% female; 17% male). METHODS: Proximal control was established in all patients through either an extracranial or petrous carotid exposure. The aneurysm was approached through a wide exposure by removing the anterior clinoid extradural. All but one aneurysm was clipped directly. A saphenous vein graft from the petrous-to-supraclinoid bypass was performed in this remaining case. RESULTS: Surgical morbidity was assessed at 20%. One patient developed a postoperative subdural hematoma and remained severely disabled. Two patients developed permanent third nerve palsy. One patient experienced severe disabling cognitive deficit. One patient died from complications related to a stroke. One patient developed transient diabetes insipidus. Visual outcome, which was assessed separately, was unimproved in 50% of the cases during a follow-up period that averaged 7 years. CONCLUSIONS: With the development of cranial base procedures such as Dolenc's combined epi- and subdural approach, large and giant aneurysms of the paraclinoid segment can be directly clipped with acceptable morbidity, allowing the ICA to remain patent.     

Olfactory bulbectomy increases prepro-galanin mRNA levels in the rat locus coeruleus

The effects of olfactory bulbectomy (OBX) on galanin (GAL) gene expression in the locus coeruleus (LC) were examined with quantitative in situ hybridization histochemistry. OBX increased prepro-GAL levels 3 and 14 days after surgery, as compared to sham-operated controls. Levels of mRNA encoding prepro-neuropeptide Y (NPY) were unchanged, and levels of mRNA encoding tyrosine hydroxylase (TH) were elevated in the LC only on day 3. The results indicate that GAL gene expression in the LC increases after lesioning a terminal field.     

Some behavioral effects of olfactory bulb damage in the rat.

Conducted 5 experiments in which male Holtzman rats (N = 50) with either olfactory bulb or septal lesions were tested on position-habit reversal, nonappetitive passive-avoidance, 1-way avoidance, and 2-way avoidance tasks. Ss with septal damage exhibited the expected behavioral abnormalities on all tasks. Ss with bulbar damage were deficient on 1-way avoidance, were facilitated on 2-way avoidance, and could not be distinguished from the normal Ss on the other 2 tasks. (20 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Olfactory cues and movement: Stimuli mediating intraspecific aggression in the wild Norway rat.

Established male sibling pairs of laboratory-bred wild rats (R. norvegicus) in enclosures and in 4 experiments observed their aggressive, amicable, and sexual behavior following the introduction of conspecifics. Intact male Ss behaved amicably toward familiar male conspecifics, both aggressively and sexually towards unfamiliar anestrous and estrous female conspecifics, and aggressively toward unfamiliar male conspecifics. Anosmic males exhibited amicable and sexual behavior toward unfamiliar males, but did not initiate aggression toward them. The storing of a member of a resident pair in a cage with or without wood shavings, urine, and feces from a foreign colony did not affect behavior toward him by his cage mate. The storing of a foreign male in the wood shavings, urine, and feces of a colony did not affect behavior of that colony toward him. Cessation of movement on the part of an intruder of either sex inhibited attack, while immobile anesthetized male intruders elicited aggression. When presented simultaneously with moving and anesthetized intruders, resident Ss attacked only the former. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Organization of inhibition in the rat olfactory bulb external plexiform layer

1. Intracellular recordings were made from the output neurons (mitral and tufted cells) of the rat olfactory bulb during electrical orthodromic stimulation of the olfactory nerve layer (ONL) and antidromic stimulation of the lateral olfactory tract and posterior piriform cortex (pPC) to test for physiological differences among the neuron types. Many of these neurons were identified by intracellular injections of biocytin, and others were identified by their pattern of antidromic activation. 2. Both marked and unmarked mitral cells showed large inhibitory postsynaptic potentials (IPSPs) in response to antidromic stimulation of the pPC, whereas tufted cells exhibited small IPSPs in response to pPC stimulation. Tufted cells, however, showed large IPSPs in response to ONL stimulation. In many cases, these tufted cell responses to ONL stimulation were larger than the mitral cell responses. The marked superficial tufted cells, those with basal dendrites in the superficial sublayer of the external plexiform layer (EPL), had the smallest IPSPs in response to pPC stimulation. These data support anatomic observations suggesting that the granule cell populations responsible for the IPSPs may be different for mitral and for superficial tufted cells. 3. The different types of output cells also showed differences in their responses to orthodromic stimulation. Type I mitral cells, which have basal dendrites confined to the deep sublayer of the EPL, were significantly less excitable by ONL stimulation than were the type II mitral cells, which have basal dendrites distributed within the intermediate sublayer of the EPL. Half of the type I mitral cells could not be excited at all by ONL stimulation. Superficial tufted cells showed even greater orthodromic excitability than type II mitral cells, usually responding to ONL stimulation with two or more spikes. 4. The ionic basis of the IPSPs in the superficial tufted cells appeared similar to those described for mitral cells. These IPSPs could be reversed by chloride injection and were associated with increased membrane conductance. 5. For both mitral and tufted cells, the number of ONL electrodes evoking IPSPs was greater than the number evoking spikes. These data suggest a kind of center-surround organization of inputs to these cells from the ONL, although this does not yet imply that the sensory receptive field of these output cells has a center-surround organization. 6. In conclusion, the properties of rat olfactory bulb output cells correlate with the sublayers of the EPL in which their basal dendrites lie.(ABSTRACT TRUNCATED AT 400 WORDS)     

Developmental modulation of mouse hypoglossal nerve inspiratory output in vitro by noradrenergic receptor agonists

The ontogeny of the noradrenergic receptor subtypes modulating hypoglossal (XII) nerve inspiratory output was characterized. Noradrenergic agents were locally applied over the XII nucleus of rhythmically active medullary slice preparations isolated from mice between zero and 13 days of age (P0-P13) and the effects on XII inspiratory burst amplitude quantified. The alpha1 receptor agonist phenylephrine (PE, 0.1-10 microM) produced a dose-dependent, prazosin-sensitive (0.1-10 microM) increase in XII nerve inspiratory burst amplitude. The magnitude of this potentiation increased steadily from a maximum of 15+/-8% in P0 mice to 134+/-4% in P12-P13 mice. The beta receptor agonist isoproterenol (0.01-1.0 mM) produced a prazosin-insensitive, propranolol-sensitive potentiation of XII nerve burst amplitude. The isoproterenol-mediated potentiation increased with development from 27+/-5% in P0-P1 slices, to 37+/-3% in P3 slices and 45+/-4% in P9-P10 slices. The alpha2 receptor agonist clonidine (1 mM) reduced XII nerve inspiratory burst amplitude in P0-P3 slices by 29+/-5%, but had no effect on output from P12-P13 slices. An alpha2 receptor-mediated inhibition of inspiratory activity in neonates (P0-P3) was further supported by a 19+/-3% reduction in XII nerve burst amplitude when norepinephrine (NE, 100 microM) was applied in the presence of prazosin (10 microM) and propranolol (100 microM). Results indicate that developmental increases in potentiating alpha1 and, to a lesser extent, beta receptor mechanisms combine with a developmentally decreasing inhibitory mechanism, most likely mediated by alpha2 receptors, to determine the ontogenetic time course by which NE modulates XII MN inspiratory activity.     

Dopaminergic modulation of olfactory bulb processing affects odor discrimination learning in rats.

Olfactory behavioral studies have shown that, when modulated through systemic injections, D1 and D2 receptors have opposing effects on odor discrimination learning. In the present study, cannulated male Sprague–Dawley rats were used to investigate how the modulation of these 2 types of dopaminergic receptors through direct infusion of D1/D2 agonists and antagonists into the olfactory bulb affect olfactory perception. Dopaminergic modulation was locally altered by manipulations of D1 (agonist SKF 82958: 14.6, 43.8, & 143.6 mM; antagonist SCH-23390: 13.4, 40.1, & 60.1 mM) and D2 (agonists quinpirole: 78.2, 117.3, & 156.4 mM; antagonist sulpiride: 0.3, 0.9, & 2.9 mM) receptors during a simultaneous odor discrimination task. The authors found that modulation of D2, but not D1, receptors significantly affected rats’ odor discrimination performance. A significant positive correlation between blockade of D2 receptors and discrimination performance, as well as a significant negative correlation between D2 receptor activation and discrimination performance, was observed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex difference and testosterone modulation of pheromone-induced NeuronalFos in the Ferret's main olfactory bulb and hypothalamus

A carnivore, the ferret possesses a vomeronasal organ--accessory olfactory bulb (VNO-AOB) projection to the hypothalamus; however, little is known about its function. Pheromones in soiled bedding from estrous female ferrets or an artificial peppermint odor significantly augmented nuclear Fos protein immunoreactivity (Fos-IR), a marker of neural activation, in several main olfactory bulb (MOB) sites but not in the AOB of gonadectomized male and females. Testosterone propionate (TP) significantly augmented the MOB's neuronal Fos responses to estrous females' pheromones, but not to peppermint. Estrous odors, but not peppermint, also augmented neuronal Fos-IR in the medial preoptic area (mPOA) of female, but not male, subjects. Pheromones in soiled bedding from breeding male ferrets significantly augmented neuronal Fos-IR in the MOB and in the medial amygdala of gonadectomized, TP-treated male and female subjects. Again, male pheromones failed to influence neuronal Fos-IR in the AOB of either sex, and only females showed significant increases in neuronal Fos-IR in the lateral aspect of the ventromedial nucleus and mPOA. These results point to an essential role among higher mammals of the main olfactory epithelium-MOB projection to the hypothalamus in detecting and processing pheromones. Gonadectomized ferrets showed significant increases in sniffing behavior when placed on either female or male bedding. This occurred regardless of whether they had received TP or oil vehicle, suggesting that testosterone's facilitation of neuronal Fos responses to estrous females' odors in the MOB of both sexes cannot be attributed to increased scent gathering. Androgen receptor-IR was present in the MOB granule cell layer of male and female ferrets, raising the possibility that testosterone acts directly on these cells to augment their responsiveness to pheromones.