Nicotine and its withdrawal alter feeding induced by paraventricular hypothalamic injections of neuropeptide Y in Sprague-Dawley rats

RATIONALE: Cigarette smoking produces feeding and weight suppression in humans that often rebound following cessation. Nicotine (NIC) administration produces similar effects in rats, but the neural mechanisms responsible are not fully known. Recent evidence shows that hypothalamic levels of neuropeptide Y (NPY) change with NIC administration. Infusions of NPY into the paraventricular nucleus of the hypothalamus (PVN), which normally produce robust feeding, were used to investigate changes in the PVN-NPY system that may contribute to NIC's effects on energy balance. OBJECTIVE: To characterize potential differences in PVN-NPY-induced feeding during NIC treatment versus withdrawal. METHODS: Three groups of female rats ( n=66) bearing unilateral PVN cannulae were implanted for 14 days with subcutaneous Alzet mini-pumps containing NIC (0, 6, or 12 mg/kg per day). Dark-onset (1800-2000 hours) NPY feeding tests occurred five times: pre-implant, 2 days and 12 days post-implant and 2 days and 8 days after implant removal. Feeding tests consisted of 1 h of pre-feeding prior to lights off, then two 1-h measures of feeding after PVN injections of 0.4 microl saline or NPY (78 pmol, 235 pmol). RESULTS: NIC initially suppressed body weight gain, followed by steady recovery that was briefly exaggerated after withdrawing NIC. Daily feeding was acutely suppressed by NIC but acutely potentiated after NIC cessation. PVN-NPY-induced feeding was suppressed by both doses of NIC 2 days after pump implant, elevated 2 days after pump removal, but returned to pre-NIC levels 8 days after pump removal. CONCLUSIONS: These findings provide behavioral support that changes in PVN-NPY neurotransmission may play a functional role in the food intake and weight-modulating effects of NIC.     

Effects of three neurochemical stimuli on delayed feeding and energy metabolism

Infusions of norepinephrine (NE), the gamma-aminobutyric acid agonist, muscimol (MUS), or neuropeptide Y (NPY) into the paraventricular nucleus (PVN) of the hypothalamus all increase food intake. Such feeding may be due to direct activation of behavioral processes driving ingestion and/or to alterations in nutrient metabolism that feeding serves to normalize. To examine these possibilities, male Sprague-Dawley rats received PVN infusions of vehicle, 20 nmol NE, 1 nmol MUS or 100 pmol NPY at dark onset, then food intake was measured under three feeding conditions: (1) 1 and 2 h immediately after injections, (2) 1 h after a 1 h delay between injections and access to food, and (3) 1 h after a 1 h feeding delay, but with injections occurring just before presenting food. Measures of energy expenditure (EE) and respiratory quotients (RQs) in the absence of food were made over 2 h in parallel experiments. Results confirmed that NE, MUS and NPY all increased dark-onset feeding, but only NPY increased intake above control levels after a 1 h feeding delay. No neurochemically-induced changes in EE were observed, nor were there changes in RQs after NE or MUS. However, NPY reliably enhanced RQs from 30 to 120 min of testing. Our findings imply that NE and MUS initiate relatively immediate, short-term feeding that is not associated with changes in nutrient metabolism and does not summate with cues stimulated by delayed access to food. NPY initiates more protracted feeding temporally linked to enhanced carbohydrate metabolism. This may indicate that part of NPY's feeding stimulatory effects are secondary to physiological processes driving ingestion.     

Dopamine-norepinephrine interactions in the development of hyperphagia and obesity following medial hypothalamic lesions

Conflicting evidence exists on the ability of central 6-hydroxydopamine (6-OHDA) injections to alter the subsequent development of hyperphagia and obesity following medial hypothalamic lesions (MHL) in rats. An initial study found no effects of prior intracisternal (IC) 6-OHDA on the subsequent development of this MHL syndrome, while later work reported that a dopamine (DA) depletions induced by intracerebral 6-OHDA effectively blocked it. The present study reexamined this issue by investigating the effects of depleting brain dopamine, norepinephrine (NE), or both DA and NE, on overeating and obesity induced by subsequent MH lesions. Different patterns of DA and NE depletions were achieved by IC 6-OHDA in combination with systemic pretreatments designed to protect central NE, DA, or neither amine, respectively. It was found that 6-OHDA regimens that selectively depleted forebrain DA did prevent the development of hyperphagia and obesity following MHL. However, when such forebrain DA depletions were accompanied by NE depletions no such blockade occurred. Manipulations which selectively depleted forebrain NE had no effect on MHL-induced hyperphagia and obesity. These results offer a framework for resolving previous discrepancies in the literature concerning brain monoamines and MHL effects. They also indicate that the effectiveness of brain DA depletions in blocking the MHL syndrome is critically dependent on the functional status of NE systems.     

Regional changes in brain 14C-2-deoxyglucose uptake after feeding-inducing intrahypothalamic norepinephrine injections

Although norepinephrine (NE) injections into the paraventricular hypothalamus (PVN) have been extensively documented to induce feeding in satiated rats, there have been few systematic attempts to elucidate the neural circuitry subserving this response. In this study quantitative 14C-2-deoxyglucose (14C-2DG) autoradiography was used to map regional brain changes induced by PVN NE injections. Male Wistar rats, bearing PVN cannulae and previously shown to be positive responders for NE-induced feeding, were given 125 microCi/kg 14C-2DG IV immediately following a PVN injection of either 40 nmol NE or vehicle, then killed 45 min later. 14C-2DG uptake was examined in 97 brain structures using computerized densitometry. PVN NE injections resulted in small, localized changes in brain 14C-2DG uptake. Forebrain structures affected included the somatosensory parietal cortex (+15%), the CA3 hippocampal field (-8%), and the reticular thalamic nucleus (+14%). Midbrain changes involved the anterior pretectal area (+8%) and the central gray area (-11%). At the hindbrain level, the lateral reticular nucleus showed the most pronounced changes of all brain regions examined (-24%), followed by the nucleus of the solitary tract (-16%) and the laterodorsal tegmental nucleus (+16%). No changes were seen in the median eminence or in other hypothalamic areas. This pattern of results largely agrees with recent proposals for the circuitry of a PVN-hindbrain system subserving NE-induced as well as hypothalamic lesion-induced feeding effects. In addition, however, they suggest the possibility that altered activity in some forebrain structures may also be involved in the NE response.     

Effects of increasing brain GABA on the meal patterns of genetically obese vs. lean Zucker rats.

To explore recent suggestions that genetically obese Zucker rats show less anorexia when brain gamma-aminobutyric acid (GABA) is elevated, obese vs. lean littermates received 100, 50 and 0 micrograms of the GABA-transaminase inhibitor, ethanolamine-O-sulfate (EOS), intra-cisternally in a longitudinal design where their feeding patterns were monitored 24 h daily. Obese rats were refractory to EOS-induced anorexia as evidenced by less suppression of daily food intake and fewer alterations to both meal size and meal frequency, particularly in the night. This effect was not due to an inability of EOS to increase brain GABA since equivalent, specific dose-dependent increments were seen in the brains of separate obese vs. lean rats after analysis of endogenous GABA and seven other amino acids. An unexpected finding was elevated levels of brain taurine for obese rats regardless of EOS dosage, implying a hitherto unknown neurochemical trait whose potential significance is unclear. The primary data obtained provide further support for recent hypotheses that obese Zucker rats possess altered brain GABAergic mechanisms that may serve as one contributor to their over-eating.     

CT demonstration of pulmonary effects of tangential beam radiation

Breast cancer is sometimes treated with an excisional biopsy and a radiation portal limited to the breast and the adjacent chest wall, especially in patients with negative lymph node dissections. The beam passes through this portion of the chest wall tangentially. Such radiation can result in changes in the included lung parenchyma that are pleural-based and sharply demarcated from the normal lung on CT lung windows. In our experience CT lung windows were more sensitive than chest radiography in showing these changes. Such changes must be recognized and differentiated from pleural metastases. Computed tomography also resulted in a more specific diagnosis than chest radiography because it better localized the abnormality to the radiation portal.     

CT characteristics of cervical mucocele mimicking a cystic adnexal mass

An unusual case of a cervical mucocele (focal hydrometra) was diagnosed only after correlation of ultrasonic, CT, and physical examination findings.     

Taming effects of handling on 6-hydroxydopamine induced ratge.

The purpose of this experiment was to determine the importance of handling to the expression of hyperemotional behaviors, i.e., rage, known to occur after chronic depletion of brain norepinephrine (NE) and dopamine (DA) following central injection of 6-hydroxydopamine (6-OHDA) in rats. Five min of handling per day for 6 consecutive days reduced resistane to capture as well as the magnitude and frequency of startle responding following one 300 mug injection of 6-OHDA intracisternally. Both 6-OHDA-handled and 6-OHDA-unhandled rats showed comparable levels of brain NE, DA, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), comparable resting levels of plasma corticosterone, and comparable adrenal weights. These data demonstrate the importance of handling to the expression of 6-OHDA-induced rage and emphasize the importance of controlling for handling as a variable which can significantly affect the assessment of rage by behavioral criteria in this animal model of hyperemotionality.     

Effects of chronic amitriptyline and desipramine on food intake and body weight in rats

Long-term treatment with tricyclic antidepressant drugs (TCAs) can induce excessive body weight gain in a significant proportion of patients. Such weight gains, which appear to be largely independent of clinical improvement, are in many cases severe enough to interfere with continuation of treatment. In efforts to model this effect in experimental animals, seven experiments were performed in which two commonly used TCAs, amitriptyline and desipramine, were administered chronically to rats. Despite manipulations of drug dosages (2.5 mg-17 mg/kg), route of administration (intraperitoneal, subcutaneous, oral; daily injections vs. continuous release from osmotic pumps), diet composition and palatability (regular Purina Chow pellets or powder with or without added high fat and high carbohydrate sources; high vs. low protein diets) and animal sex and housing conditions (single vs. group housing), chronic TCA treatment was never observed to increase daily food intake or rates of body weight gain. Desipramine treatment invariably caused decreased food intake and weight loss. Amitriptyline treatment either caused no change in food intake and body weight or slightly reduced levels in comparison to vehicle-treated controls. However, both amitriptyline- and desipramine-treated rats showed a potentiation of acute caloric intake after a single systemic injection of the glucoprivic agent 2-deoxy-D-glucose. These results are considered against the background of human clinical observations. Possible reasons for the differences between human and animal data are discussed.