Biomedical subjects

T Baptista

Publications and source records attributed to T Baptista.

At least 37 records · Page 2Linked to original sources

PubMed1998

Glucose tolerance and serum insulin levels in an animal model of obesity induced by the antipsychotic drug, sulpiride.

To assess the role of insulin in the development of obesity induced by antipsychotic drugs, a glucose tolerance test was conducted in 40 female rats during the peak of sulpiride-induced weight gain and in 40 vehicle-treated animals. The glucose area under the curve did not differ between the groups (P = 0.24), however, the area under the insulin curve was significantly decreased by sulpiride (55.2 +/- 2.8 versus 115.6 +/- 18.9, P = 0.007). The results suggest that insulin resistance and hyperinsulinaemia are not involved in the excessive weight gain observed in this animal model of drug-induced obesity. Alternatively, the insulin-dampened response observed in the sulpiride-treated rats may be related to increased insulin sensitivity, which may promote weight gain as proposed by Ravussin (1995).

Animals↗

PubMed1997

Effects of lithium carbonate on reproductive hormones in healthy men: relationship with body weight regulation--a pilot study.

1. To test the hypothesis that lithium-induced body weight gain is related to an unbalance in the reproductive hormones, lithium carbonate (900 mg/day) or placebo was administered to healthy men for 1 month. 2. Body weight, skin folds and the serum levels of thyrotropic hormone, tetraiodothyroxine, prolactin, follicle-stimulating hormone, luteinizing hormone, testosterone (T5), dehydroepiandrosterone sulfate (DHEAS), estradiol (E2), cortisol, the ratios E2/T5 and T5/DHEA-S, and blood lipids were evaluated before and during treatment. 3. Body weight, skin folds, hormones and lipids serum levels were not significantly affected by the treatment with Li. These results agree with previous reports of lack of effects of 1 month-Li administration on appetite and body weight in normal male subjects (Chen et al., 1992), and question the appropriateness of studying Li-induced obesity in healthy volunteers, given the short-term administration and low doses of Li that must be used.

Adult↗

PubMed1997

Amantadine in the treatment of neuroleptic-induced obesity in rats: behavioral, endocrine and neurochemical correlates.

The efficacy of the antiviral agent Amantadine (AM, 5-100 mg/kg/sc, ip or intrahypothalamically, 12.5-100 micrograms bilaterally) in influencing body weight and food intake in drug-free rats, and in preventing neuroleptic-induced weight gain, was assessed in adult female rats. In drug-free rats, acute administration of systemic AM or directly injected in the lateral hypothalamus (LH) displayed a significant dose-dependent anorectic effect (p < 0.001). This effect could be mediated by the brain monoaminergic system, because systemic or local injections of AM increased dopamine and serotonin overflow in the nucleus accumbens and in the LH. Chronic administration of AM significantly decreased body weight gain in drug-free rats only at the dose of 100 mg/kg/sc. Similarly, obesity induced by the neuroleptic drug sulpiride (SUL, 20 mg/kg/ip for 21 days) was prevented by AM only at the dose of 100 mg/kg. AM did not prevent SUL-induced hyperprolactinemia, disruption of the vaginal cycle and a decrement in the weight of the uterus and ovaries at any dosage. This lack of efficacy of AM contrasts with that of bromocriptine, which completely prevented SUL-induced weight gain and hyperprolactinemia. The results show that despite a potent acute anorectic effect, AM displays a weak antagonistic action on SUL-induced obesity in rats, in contrast to the preliminary results obtained in humans. As AM metabolism differs in humans and rats, additional research is needed before its systematic testing in counteracting neuroleptic-induced obesity in patients with mental disorders.

Amantadine↗

PubMed1997

Effects of the antipsychotic drug sulpiride on reproductive hormones in healthy men: relationship with body weight regulation.

Metabolic and endocrine abnormalities secondary to hyperprolactinemia, particularly hypogonadism, may be involved in the excessive body weight gain observed during treatment with antipsychotic drugs. The present study was conducted in healthy men in order to detect an endocrine imbalance secondary to antipsychotic drug administration, which, if sustained in the long term, might be involved in the development of obesity. Sulpiride (200 mg daily for 30 days) or placebo was nonblindly administered, and body weight gain was correlated with the serum levels of prolactin, luteinizing hormone, follicle-stimulating hormone, estradiol, free testosterone, thyrotropic hormone, free tetraiodothyroxine, cortisol, dehydroepiandrosterone sulphate (DHEA-S), and the ratios estradiol/testosterone and testosterone/DHEA-S; the blood lipids were also assessed. Body weight gain and the serum levels of prolactin were significantly increased by sulpiride; in addition, a significant positive correlation was observed between prolactin levels and body weight gain. Other endocrine parameters were not significantly affected by the drug. These short-term results show that in healthy men, body weight can be increased by antipsychotic drug administration; this effect may be related to hyperprolactinemia alone, since other endocrine parameters were normal at the time of treatment. A more prolonged treatment with antipsychotic agents might be required to observe the alterations in gonadal and adrenal steroids often detected in subjects with primary obesity.

Adult↗

PubMed1997

Effects of the antipsychotic drug sulpiride on reproductive hormones in healthy premenopausal women: relationship with body weight regulation.

Metabolic and endocrine abnormalities secondary to hyperprolactinemia, such as hypogonadism and hyperandrogenicity, may be involved in the excessive body weight gain induced by antipsychotic drugs in women. The present study was conducted in healthy premenopausal women, in order to detect an endocrine imbalance secondary to antipsychotic drug administration, which, if sustained in the long term, might be involved in the development of obesity. After a control menstrual cycle, sulpiride (200 mg/day) or placebo was nonblindly administered for 28 days; blood lipids and the serum levels of the following hormones which are involved in body weight regulation were assessed at days 3, 10, 20 and 26 of the cycle: prolactin (PRL), 17-beta estradiol (E2), progesterone (P4), follicle stimulating hormone (FSH), luteinizing hormone (LH), free testosterone (T5), dehydroepiandrosterone sulfate (DHEAS), cortisol, tyrotropic hormone (TSH), tetraiodothyroxine (T4), and the areas under the insulin and glucose tolerance curve. During sulpiride administration, the following changes were observed when compared to placebo administration: PRL levels were significantly increased; E2 levels were significantly reduced at days 10 and 20; P4 levels were significantly reduced at day 20, and the area under the glucose tolerance curve was significantly increased. The other variables were not significantly affected. The body weight gain was higher during sulpiride than during placebo administration, but it did not reach statistical significance, perhaps because the period of treatment was too short. The decrease in the serum levels of E2 during sulpiride administration is probably secondary to hyperprolactinemia. It affects the E2/T5 ratio in the direction of increasing the androgenic activity, as observed in women with well-established obesity. This effect, along with a genetic predisposition, increased appetite, hypoactivity and ignorance of proper dietary habits, may explain the excessive weight gain and obesity observed in women during chronic treatment with sulpiride and other antipsychotic agents.

Adult↗

PubMed1996

Systemic and local cocaine increase extracellular serotonin in the nucleus accumbens.

The effect of systemic or intra-accumbens injections of cocaine on serotonin (5-HT) overflow was studied by nucleus accumbens microdialysis in freely moving rats. In Experiment 1, cocaine was injected intraperitoneally at 0, 10, 20, and 30 mg/kg. In Experiment 2, cocaine (3.6, 7.2, and 14.4 mM), lidocaine (7.2 mM), or saline was infused through the probe by reverse microdialysis. Extracellular serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were measured by high-pressure liquid chromatography and electrochemical detection. Systemic administration of cocaine induced a dose-related increase in 5-HT overflow and a decrease of 5-HIAA. Intra-accumbens cocaine infusion also caused a dose-related increase in 5-HT, but no effect on 5-HIAA. As a control for local anesthesia, equimolar lidocaine did not increase 5-HT. The difference between lidocaine and cocaine was not due to unequal diffusion out of the probe, because previous in vivo calibration of the probe showed that more lidocaine than cocaine diffused out of the probe when equimolar solutions were infused. These experiments suggest that systemic cocaine acts on the nucleus accumbens to increase synaptic 5-HT.

Animals↗

PubMed1995

The teaching of the biological basis of psychiatry.

1. What is usually taught as biological psychiatry in psychiatric residency training is mainly psychopharmacology, but biology has a lot more to offer to psychiatry educators. 2. The main thesis of this article is that an introductory course on the applications to psychiatry based on the theory of the evolution of the species by natural selection and mutation, along with a comprehensive theory of mind, may contribute to: (i) helping young physicians to integrate the diverse and extensive knowledge acquired during the residency training; (ii) aid in keeping the psychiatrist within the medical approach to mental illnesses while promoting the specific features of the specialty, and (iii) perhaps developing a general theoretical framework that allows psychiatrists to maintain a prominent role in the mental health staff. 3. The author describes how he has conducted such training in Venezuela. It is expected that the author's ideas will serve as a forum for discussion of this pivotal subject.

Animals↗

PubMed1995

Lithium and body weight gain.

Weight gain is an undesirable side-effect of long-term lithium administration which notably interferes with treatment compliance. The mechanisms of this weight gain remain unclear, making its management in patients difficult. In this paper, studies describing the features of this weight gain in patients and in rats treated with chronic lithium administration are reviewed. The effects of lithium on body weight differ between patients and rats in a number of ways, including the observation that excessive weight gain is observed in both male and female patients, but only in female rats. Nevertheless, an animal model of lithium-induced weight gain may be able to provide useful insights into some of the specific mechanisms involved, particularly those related to interactions with gonadal steroid function. We discuss the effects of lithium on the endocrine system, neurotransmitters, metabolism, electrolyte regulation, and feeding behavior, which might underlie lithium's effects on body weight. Finally, suggestions for the management of weight gain in the clinical setting are presented. These include, in the long term, dietary control and physical activity and, in the short term, choosing among several drugs that have been tested either in patients or in animal models of obesity. If weight gain still cannot be controlled and treatment compliance is at risk, the mood stabilizers carbamazepine or valproic acid might be substituted for lithium treatment.

Animals↗

PubMed1994

Testosterone modulates mesolimbic dopaminergic activity in male rats.

Male rats were castrated before puberty. When they were adult, the activity of their mesolimbic dopamine system was tested by ventral striatum microdialysis. Amphetamine injections increased dopamine more in castrated rats than in normal rats. This exaggerated response was attenuated by testosterone replacement therapy. The mechanism by which androgens modulate the activity of the mesolimbic dopamine system is discussed.

Amphetamine↗

PubMed1994

Electrical kindling is associated with increases in amygdala acetylcholine levels: an in vivo microdialysis study.

Using brain microdialysis, acetylcholine (Ach) levels were assessed in the nucleus amygdaloideus lateralis of electrically kindled rats using a cholinesterase inhibitor in the perfusion fluid to prevent Ach breakdown. During kindling development, when the animals displayed afterdischarges lasting more than 30 s but no seizures, a significant increase in Ach levels (+66%) was observed after electrical stimulation. Ach levels were also elevated after a stage 5 kindled seizure (+48%), with no additional increment compared to rats experiencing only afterdischarges. Chronic diazepam administration prevented kindling development and the increment in Ach overflow; however, diazepam itself (following acute administration) tended to decrease Ach levels in the amygdala. These findings are convergent with pharmacological data suggesting that changes in the cholinergic function may be important especially during amygdaloid kindling development.

Acetylcholine↗

PubMed1994

Dopamine increase in the prefrontal cortex correlates with reversal of haloperidol-induced catalepsy in rats.

The mechanism by which forced swimming reverses, haloperidol-induced catalepsy was examined by measuring dopamine (DA) turnover in the nucleus accumbens-ventromedial caudate (NAC-C) and the prefrontal cortex (PFC) in rats. DA and its metabolites 3,4-dihydroxiphenylacetic acid (DOPAC) and homovanillic acid (HVA) were assessed by microdialysis and high pressure liquid chromatography with electrochemical detection (HPLC-ED) after systemic administration of a cataleptic dose of haloperidol (5 mg/kg) or saline. Haloperidol-induced catalepsy was temporarily suppressed by forced swimming. Haloperidol-treated rats showed an increase of DA, DOPAC, and HVA overflow in the PFC and the NAC-C. This increase was greater in the PFC of rats that were forced to swim. Rats that were not treated with haloperidol but were forced to swim (control group) showed an increase of DA, DOPAC, and HVA in the PFC but not in the NAC-C. Zero micrograms, 5 micrograms, 10 micrograms, and 20 micrograms of DA was bilaterally injected in the PFC of cataleptic rats to evaluate the hypothesis that DA in the PFC reverses catalepsy. Haloperidol-induced catalepsy was diminished by bilateral microinjections of 10 micrograms and 20 micrograms but not by 5 micrograms of DA in the PFC. The higher the dose of DA, the longer the decrease of catalepsy. These results suggest that an increase of DA turnover in the PFC might mediate temporal suppression of haloperidol-induced catalepsy. The mechanism by which the mesocortical DA system reduces catalepsy is discussed.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Substance use among Venezuelan medical and pharmacy students.

The frequency of substance use disorders and non-pathological use of drugs was assessed in a cohort of undergraduate medical (N = 1013) and pharmacy students (N = 426) from the University of the Andes (Mérida, Venezuela). The survey was conducted using a self-administered Spanish version of the Diagnostic Interview Schedule (DIS-III-A). It was found that the lifetime frequency of substance use disorders was significantly higher in medical than in pharmacy students, but this difference disappeared when the sex was controlled. Substance use disorders were more common in single males and most cases were observed in subjects in their intermediate academic semesters. It was also found that the frequency of non-pathological use of drugs was higher in medical than in pharmacy students and in men than in women. The frequency of substance use disorders in our sample was smaller than that reported in American surveys of substance misuse among medical and pharmacy students. However, because of methodological differences these comparisons are questionable. Our results suggest that Venezuelan medical students are not at an unusually high risk of substance misuse when compared with pharmacy students whose reputedly low levels of substance use are often contrasted with those of the medical profession.

Adult↗

PubMed1994

Hyponatremia and neuroleptic-induced obesity in rats.

The weight gain and hyperphagia induced by chronic administration of sulpiride in female rats were not prevented by the concomitant administration of an extra source of sodium. In addition, serum sodium levels were not affected, but potassium levels were significantly reduced by sulpiride administered for 1 week. These results suggest that sulpiride-induced obesity in rats is not related to sodium imbalance. The mechanism for the decrease in serum potassium levels and its relation with sulpiride-induced weight gain warrant further investigation.

Animals↗

PubMed1993

Carbamazepine attenuates cocaine-induced increases in dopamine in the nucleus accumbens: an in vivo dialysis study.

Carbamazepine's effects on cocaine-induced increases in dopamine overflow in the nucleus accumbens were studied using in vivo microdialysis in anesthetized rats. Rats were chronically treated with a diet containing carbamazepine or no drug for one week prior to microdialysis procedures. The basal levels of dopamine in the nucleus accumbens did not differ between groups; however, the increases in dopamine following cocaine administration (4 mg/kg i.v.) were significantly reduced by carbamazepine. In addition, basal levels of dihydroxyphenyl acetic acid (DOPAC) were significantly diminished in the carbamazepine group and a trend in the same direction was observed for homovanilic acid (HVA). These results are consistent with reports that carbamazepine might decrease dopamine synthesis. Further studies are required to determine the mechanism of carbamazepine's inhibition of cocaine-induced dopamine overflow and its potential clinical implications.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Effects of acute and chronic lithium treatment on amphetamine-induced dopamine increase in the nucleus accumbens and prefrontal cortex in rats as studied by microdialysis.

The effects of acute and chronic administration of lithium (Li) on the basal levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxy-indoleacetic acid (5-HIAA), and the amphetamine-induced DA increase were assessed in the Nucleus Accumbens (NAC) and Prefrontal Cortex (PFC) by brain dialysis in freely-moving rats. Acute Li (2 meq/L) was locally administered by reverse dialysis. Chronic Li (2 meq/kg) was intragastrically administered for 14 days. No effect was observed after acute Li administration. However, after chronic Li administration, the basal levels of DOPAC and the amphetamine-induced DA increase in the NAC were significantly higher in the Li-treated rats than in the saline-treated controls. In the PFC, while the amphetamine-induced DA increase was not affected by chronic Li, the basal levels of DA and DOPAC were significantly decreased after Li administration. The effects of chronic Li in the NAC could be due to increased synthesis and/or decreased release of DA, whereas in the PFC the effects could be due to a decreased synthesis of DA. The absence of effects of acute Li administration is in agreement with the therapeutic inefficacy of the acute use of the cation. The changes observed after chronic treatment in the NAC and the PFC could be related to the effects of Li on mood disorders and cognitive functions, respectively.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Enhancement of amphetamine anorexia after chronic administration of sulpiride in rats.

Long-term administration of sulpiride induces hyperphagia and obesity in female rats. After sulpiride withdrawal, a significant hypophagia has been observed. The hyperphagia could be related to the blockade and the hypophagia to supersensitivity of dopamine D2 receptors, in particular those D2 receptors located in the perifornical hypothalamus. If this were the case, an enhancement of anorexia induced by amphetamine and dopamine should be observed after interruption of long-term sulpiride treatment. Two doses of systemic sulpiride (20 or 200 mg/kg) and one dose of intrahypothalamic sulpiride (15 micrograms) were tested. Amphetamine was administered by systemic or intrahypothalamic infusion. Dopamine was administered in the hypothalamus. After withdrawal of systemic administration of sulpiride (200 mg/kg), an enhancement of anorexia induced by systemic amphetamine was observed. However, the anorexia induced by intrahypothalamic injections of amphetamine or dopamine was not affected by the interruption of the sulpiride treatment. These results suggest that the hypophagia following chronic sulpiride treatment is not due to supersensitivity of D2 dopamine receptors in the lateral hypothalamus. Moreover, the change in the response to amphetamine might be related to supersensitivity of extrahypothalamic D2 receptors.

Amphetamine↗

PubMed1993

Effects of long-term administration of clozapine on body weight and food intake in rats.

Previous reports have shown that long-term administration of typical and atypical neuroleptics induced obesity in female but not in male rats. It has been suggested that impaired ovarian steroidogenesis related to neuroleptic-induced hyperprolactinemia is necessary to observe the body weight changes. This hypothesis was tested with clozapine, an atypical neuroleptic that produces in rats a shorter increase in serum prolactin levels than do other neuroleptics. The effects of clozapine on body weight and food intake were assessed in female and male rats under treatment with any of the following doses: 0.5, 1, 2.5, 5, 10, and 20 mg/kg IP for 21 days. Vaginal cycle under clozapine treatment, as an indirect indicator of ovarian steroidogenesis, was also assessed. Obesity was not observed in any group. By contrast, clozapine at the doses of 10 and 20 mg/kg significantly decreased body weight and feeding in male rats. Clozapine at the doses of 5 and 10 mg/kg IP induced permanent diestrus. The failure of clozapine to induce obesity in female rats, despite impaired vaginal cycle, can be considered indirect evidence that drug-induced hyperprolactinemia is not sufficient to observe neuroleptic-induced obesity in rats.

Animals↗

PubMed1993

Substance use among resident doctors in Venezuela.

This study was aimed to develop a self-administered questionnaire to detect substance use disorders based on the Spanish version of the Diagnostic Interview Schedule (DIS) and to evaluate the frequency of substance abuse and/or dependence among resident physicians of a large university hospital in Venezuela. The questionnaire showed a high concordance with the clinical diagnoses. Frequency of substance abuse and dependence was evaluated among 191 resident doctors. The frequencies of lifetime diagnoses were: tobacco dependence: 20.9%; alcohol abuse: 11%; alcohol dependence: 0.5%; drug abuse: 1% and drug dependence: 1%; non-pathological use of drugs: 20.4%.

Adult↗