Fluoxetine prevents 8-OH-DPAT-induced hyperphagia in Fischer inbred rats.

Ovariectomized, Fischer rats were hormonally primed with 10 μg estradiol benzoate and 50 μg progesterone or were treated with the sesame seed oil vehicle. Food intake was measured 2 h and 24 h after treatment with 0.25 mg/kg of the 5-HT(1A) receptor agonist, (±)-8-hydroxy 2-(di-n-propylamino) tetralin (8-OH-DPAT), 5 mg/kg of the selective serotonin reuptake inhibitor, fluoxetine, or their combination.

Progesterone reduces the effect of the serotonin 1B/1D receptor antagonist, GR 127935, on lordosis behavior.

Ovariectomized rats were hormonally primed with 10 microg estradiol benzoate or with estradiol benzoate plus 500 microg progesterone. Rats received a bilateral infusion with 200 ng of the 5-HT(1B/1D) receptor antagonist, N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-1-1'-biphenyl-4-carboxamide hydrochloride (GR 127935), into the ventromedial nucleus of the hypothalamus (VMN), followed by a 5 min restraint or home cage experience. In estrogen-primed females that had experienced minimal handling between ovariectomy and use in the experiment, infusion with the water vehicle transiently inhibited lordosis behavior, and the 5-HT(1B/1D) receptor antagonist amplified this inhibition.

Modest effects of repeated fluoxetine on estrous cyclicity and sexual behavior in Sprague Dawley female rats.

In an earlier study, we reported that daily fluoxetine treatment (10 mg/kg/day) rapidly disrupted estrous cyclicity and sexual receptivity in adult, regularly cycling Fischer rats. The current study was designed to investigate if comparable fluoxetine treatment would similarly affect intact, regularly cycling Sprague Dawley rats. In the first experiment, fluoxetine was injected for 24 days.

Daily male exposure attenuates estrous cycle disruption by fluoxetine.

Fluoxetine (Prozac) produces sexual dysfunction in a substantial number of patients. In the few animal studies designed to address this sexual dysfunction in females, data have been inconsistent. Some investigators report that the drug disrupts sexual behavior without affecting the estrous cycle while we have reported robust effects of fluoxetine on the estrous cycle.

The role of the selective serotonin reuptake inhibitor fluoxetine in temperature regulation in ovariectomized rat models.

Thermoregulation is an integrated network of neuroendocrine, autonomic and somatosensory responses. Thermoregulatory dysfunction occurs during fluctuations or decline of gonadal hormone levels and results in vasomotor symptoms such as hot flushes and/or night-time sweating. The neurotransmitter serotonin (5-HT), has been reported to play a role in thermoregulation via changes in extracellular 5-HT levels and/or activation of various 5-HT receptors.

Effects of the 5-HT2A antagonist mirtazapine in rat models of thermoregulation.

Thermoregulation is a complex intercommunicative function requiring coordination between core body temperature (CBT), the central nervous system, and peripheral vasculature. In menopausal women, dysregulation of thermoregulatory mechanisms leads to hot flushes and night sweats. A previous study in ovariectomized (OVX) rats has suggested that mirtazapine can alleviate thermoregulatory dysfunction by blocking 5-HT(2A) receptor signaling.

Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson's disease.

We report that a low-calorie diet can lessen the severity of neurochemical deficits and motor dysfunction in a primate model of Parkinson's disease. Adult male rhesus monkeys were maintained for 6 months on a reduced-calorie diet [30% caloric restriction (CR)] or an ad libitum control diet after which they were subjected to treatment with a neurotoxin to produce a hemiparkinson condition. After neurotoxin treatment, CR monkeys exhibited significantly higher levels of locomotor activity compared with control monkeys as well as higher levels of dopamine (DA) and DA metabolites in the striatal region.

Effects of chronic intraputamenal infusion of glial cell line-derived neurotrophic factor (GDNF) in aged Rhesus monkeys.

In this study, 17-23 year old Rhesus monkeys were used as an early model of Parkinson's disease (PD). Four animals received chronic infusions of GDNF and four received vehicle infusions into the right putamen via programmable pumps for 8 weeks. Weekly videotaping was performed to record general motor performance and a monkey movement analysis panel (mMAP) was used to quantify fine and coarse upper limb motor performance.

Chronic, controlled GDNF infusion promotes structural and functional recovery in advanced parkinsonian monkeys.

The powerful trophic effects that glial cell line-derived neurotrophic factor (GDNF) exerts on midbrain dopamine neurones suggest its use in treating Parkinson's disease. However, some important questions remain about the possible therapeutic applications of GDNF. Here we demonstrate that the chronic infusion of 5 or 15 micro g/day GDNF into the lateral ventricle or the striatum, using programmable pumps, promotes restoration of the nigrostriatal dopaminergic system and significantly improves motor functions in rhesus monkeys with neural deficits modelling the terminal stages of Parkinson's disease.

How does the brain control lifespan?

There is generally a positive correlation between brain/body size ratio and lifespan, particularly among mammals, suggesting a role for the brain in determining lifespan. Recent studies in diverse organisms including nematodes, flies and rodents have provided evidence that, indeed the brain may control lifespan. Signaling pathways involved in both central nervous system and peripheral stress responses and regulation of energy metabolism may play important roles in lifespan determination.