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Athina Markou

Publications and source records attributed to Athina Markou.

65 records · Page 4Linked to original sources
PubMed2002

Both the shell of the nucleus accumbens and the central nucleus of the amygdala support amphetamine self-administration in rats.

Intracranial self-administration of drugs offers the opportunity to localize the neuronal substrates mediating the rewarding effects of drugs. The purpose of the present study was to explore whether the nucleus accumbens shell and the central nucleus of the amygdala, two components of the "extended amygdala," would support self-administration of the psychostimulant amphetamine. Male Wistar rats were trained to lever press under a Fixed Ratio 1 schedule of reinforcement for D-amphetamine injections (0, 1.0, 1.5, 2.0 and 3.0 microg/microl/inj) into either the nucleus accumbens shell or the central nucleus of the amygdala. An ascending limb dose-response function with peak responding at the 2.0 microg/microl/inj dose was obtained for self-administration at both brain sites. These results indicate that monoaminergic transmission in both the nucleus accumbens shell and the central nucleus of the amygdala mediates the rewarding effects of amphetamine. Further, the present study provides additional evidence about the functional homogeneity of the forebrain continuum called the "extended amygdala."

Amphetamine↗
PubMed2002

Assessing antidepressant activity in rodents: recent developments and future needs.

Animal models are indispensable tools in the search to identify new antidepressant drugs and to provide insights into the neuropathology that underlies the idiopathic disease state of depression. As new targets are developed, both serendipitously and through hypothesis-driven research, existing animal paradigms are being modified and new tests are being developed to detect antidepressant actions of compounds acting on a broad range of neural and genetic targets. This review focuses on recent findings regarding some of the most widely employed animal models used currently to predict antidepressant potential. Emphasis is placed on recent modifications to such paradigms that have increased their utility and reliability. Furthermore, some key issues that need to be addressed for future discovery of novel antidepressant agents are examined, and the available data on genetically altered mice that might lead to the discovery of novel targets for antidepressant action are collated.

Animals↗
PubMed2002

A 'crash' course on psychostimulant withdrawal as a model of depression.

Most drugs of abuse generate diverse behavioral and neurochemical effects in mammals. However, one feature common to many such drugs is the phenomenon of the withdrawal syndrome that results from termination of drug administration. Early drug withdrawal, often referred to as the 'crash' phase in humans, is characterized by adverse psychological and/or somatic symptoms. Withdrawal from psychostimulant drugs precipitates a transient and primarily psychological condition that bears remarkable similarity to the symptoms of major depressive disorder in humans. Rodent paradigms of psychostimulant withdrawal faithfully model the human condition. Associated behavioral deficits in these animals can be reversed by treatments with antidepressant properties, suggesting that psychostimulant withdrawal might provide the basis for an animal model of depression. Current advances and limitations in the development of this model, together with recent evidence that psychostimulant withdrawal in rodents can be used to screen for novel, rapidly acting antidepressant treatments, are discussed.

Animals↗
PubMed2002

Neurobiological evidence for hedonic allostasis associated with escalating cocaine use.

A paradoxical aspect of the transition to drug addiction is that drug users spend progressively more time and effort to obtain drug hedonic effects that continually decrease with repeated experience. According to the hedonic allostasis hypothesis, increased craving for and tolerance to the hedonic effects of drugs result from the same chronic alteration in the regulation of brain reward function (allostasis). Here we show in rats that repeated withdrawals from prolonged cocaine self-administration produces a persistent decrease in brain reward function that is highly correlated with escalation of cocaine intake and that reduces the hedonic impact of cocaine.

Animals↗
PubMed2002

Neuroadaptations to chronic exposure to drugs of abuse: relevance to depressive symptomatology seen across psychiatric diagnostic categories.

Depressive symptomatology is expressed across a wide spectrum of psychiatric disorders including major depression and schizophrenia. Further, depressive symptomatology is also observed in individuals undergoing withdrawal from chronic exposure to various drugs of abuse including cocaine, amphetamine and nicotine. The negative affective state associated with drug withdrawal is phenomenonologically similar to that observed in depressed and schizophrenia patients suggesting that common underlying pathophysiological deficits may be involved in the depressive symptomatology seen across these different psychiatric disorders. The aim of the present review is to examine clinical and preclinical evidence in support of a common neurobiological substrate mediating the negative affect associated with different psychiatric illnesses. First, clinical and epidemiological data are presented demonstrating the high comorbidity between nicotine and psychostimulant dependence, and depression or schizophrenia. It is hypothesized that drug-use may represent an attempt to self-medicate an underlying negative affective state present in depressed and schizophrenia patients. Second, preclinical findings are presented that demonstrate common neurochemical deficits in drug withdrawal and depression. Taken together, these clinical and preclinical data support the hypothesis that common neurobiological substrates may mediate the depressive state observed across psychiatric diagnostic categories. Therefore, it is proposed that the study of drug-induced depressions in laboratory animals may have heuristic value in identifying the mechanisms underlying the depressive symptomatology associated not only with drug withdrawal but also major depression and schizophrenia.

Journal Article↗
PubMed2001

Nicotine potentiation of brain stimulation reward reversed by DH beta E and SCH 23390, but not by eticlopride, LY 314582 or MPEP in rats.

RATIONALE: Systemic nicotine administration increases dopamine and glutamate levels in reward-related brain areas. Nicotine-induced increases of dopamine in the nucleus accumbens are in part mediated by glutamatergic projections to the ventral tegmental area dopamine neurons. OBJECTIVES: To assess the effects of actions at acetylcholine, dopamine, presynaptic (mGluR(2/3)) and postsynaptic (mGluR(5)) metabotropic glutamate receptors (mGluRs) on the potentiation of brain stimulation reward induced by systemically administered nicotine (0.125-0.5 mg/kg; free base) in rats. METHODS: A discrete-trial current-threshold s stimulation reward procedure (electrodes placed in the posterior lateral hypothalamus) was used to assess the effects of DH beta E (0.5-5 mg/kg), an acetylcholine nicotinic receptor antagonist, SCH 23390 (1.25-5 microg/kg), a dopamine D(1) receptor antagonist, eticlopride (2.5-20 microg/kg), a dopamine D(2) receptor antagonist, LY 314582 (1-20 mg/kg), an mGluR(2/3) agonist, and MPEP (1-9 mg/kg), an mGluR(5) antagonist, on the reward potentiating effects of nicotine (0.25 mg/kg). RESULTS: DH beta E had no effect on reward thresholds when administered alone, but dose-dependently reversed the nicotine-induced potentiation of brain stimulation reward. SCH 23390 (5 microg/kg) elevated thresholds when administered alone, and reversed the nicotine-induced potentiation of brain stimulation reward even at a dose (2.5 microg/kg) that had no effect on reward thresholds. Eticlopride (10-20 microg/kg), LY 314582 (10-20 mg/kg) and MPEP (9 mg/kg) elevated thresholds when administered alone but had no effect on the nicotine-induced potentiation of brain stimulation reward. CONCLUSIONS: These results indicate that nicotinic and dopamine D(1) receptors are involved in the nicotine-induced potentiation of brain stimulation reward, while actions at dopamine D(2), mGlu(2/3) and mGlu(5) receptors did not modulate this effect of nicotine.

Animals↗
PubMedDate not supplied

Estrogens and brain function.

Cognitive decline is well recognized during ageing but is often accelerated in women after menopause. Studies have shown that there are significant gender differences in brain ageing with significantly greater changes in brain structure, function and metabolism between females and males. Estrogens exert protective effects on neuronal cells in culture but the exact underlying mechanism for their neuroprotective effect in humans is not completely understood. Estrogens have been shown to affect the nervous system in many different ways: via binding to estrogen receptors (ERs) but also via multiple pathways. The results of small randomized trials and larger observational studies suggest a beneficial effect of estrogen therapy on cognitive function in symptomatic postmenopausal women. However, the results of the Women's Health Initiative Study (WHIMS) do not support this, at least not in women over the age of 65. Alzheimer's disease (AD) is two to three times more common in women than in men. Based on currently available data, routine therapeutic use of estrogens in women with AD is not justified but it may have a role in the prophylaxis of AD. The existing evidence supports the use of HRT only in women with menopausal symptoms for a few years following menopause.

Aged↗
PubMedDate not supplied

A unique case of a benign adrenocortical tumor with triple secretion of cortisol, androgens, and aldosterone: development of multiple sclerosis after surgical removal of the tumor.

We present a 39-year old female with a benign adrenal tumor characterized by autonomous secretion of cortisol, androgens, and aldosterone. The patient presented with a 4-year history of hypertension and severe hirsutism. Baseline investigations revealed elevated testosterone, androstendione, and 17OH progesterone with normal levels of dehydroepi androsterone sulfate. CT of the adrenals revealed a 2.5 x 3.0 cm tumor with characteristics of an adenoma on the left adrenal gland. Pelvic ultrasound was normal. Further investigations revealed suppressed basal ACTH levels, loss of diurnal rhythm of cortisol, and failure to suppress on low dose dexamethasone suppression test, suggesting autonomous cortisol secretion by the tumor. She had an exaggerated response of 17OH progesterone to ACTH, implying reduced 21-hydroxylase activity. An elevated plasma aldosterone concentration to plasma renin activity ratio was suggestive of hyperaldosteronism, which was confirmed by failure of aldosterone to suppress to a formal saline infusion test. Complete clinical and biochemical remission of the disease was observed after left adrenalectomy. Histology confirmed the presence of an adrenocortical adenoma. The patient developed multiple sclerosis 6 months after the operation. The flare-up of an autoimmune disease (multiple sclerosis) postoperatively could be coincidental or possibly related to the high normalization of the high cortisol levels acting as a precipitating factor.

Adrenal Cortex Neoplasms↗
PubMedDate not supplied

Laparoscopic surgery for adrenal tumors. A retrospective analysis.

OBJECTIVE: Laparoscopic adrenalectomy has rapidly replaced open adrenalectomy as the procedure of choice for benign adrenal tumors. The aim of this study was to evaluate the short- and long-term results of 100 consecutive laparoscopic and open adrenalectomies performed during a period of 8.5 years in our Surgical Unit. DESIGN: A retrospective analysis of patients operated on for adrenal tumors was conducted. From May 1997 to August 2005, one hundred adrenalectomies were performed on 95 patients. Five patients underwent either synchronous or metachronous bilateral adrenalectomy. There were 38 men and 57 women, aged 16 to 80 years. The size of tumors in our series ranged from 3.2 to 27 cm. The largest laparoscopically excised tumor was a ganglioneuroma with a diameter of 13 cm. RESULTS: In 73 patients laparoscopic procedure was completed successfully. In 8 cases the laparoscopic procedure was converted to open. Fourteen patients were treated with open approach. One patient with pheochromocytoma succumbed following pulmonary embolus. In one patient with morbid obesity, Cushing's syndrome, and bilateral adrenal macronodular hyperplasia, the left laparoscopic adrenalectomy was complicated by a low output pancreatic fistula, conservatively treated. All other patients had an uneventful course. Operative time for laparoscopic adrenalectomies ranged from 65 to 180 minutes. The average postoperative hospital stay for laparoscopic adrenalectomy ranged from 1 to 2 days (1.5 days), versus 5 to 20 days for patients who underwent open or converted procedure. CONCLUSIONS: Laparoscopic adrenalectomy should be the treatment of choice for all benign adrenal tumors. Laparoscopic resection of large adrenal tumors necessitates experience in open surgery and advanced laparoscopic surgery.

Adolescent↗
PubMedDate not supplied

Testicular leydig cell tumor presenting as primary infertility.

A 29-year old male and his wife presented with an 18 month history of primary infertility. History and initial investigations suggested no major female pathologic component but a semen analysis revealed azoospermia. There was no history of any sexual dysfunction and neither partner was receiving any medication. Clinical examination revealed normal secondary sexual characteristics. Both testicles were of normal consistency with a volume of approximately 15 ml but a 4 x 2 cm mass was palpable at the lower pole of the left testis. Laboratory investigations revealed: serum testosterone 37.1 nmol/l (NV:10.0-38.0 nmol/l), LH<0.3 U/L (NV:3.0-12.0 U/L), and FSH <0.1 IU/L (NV:3.0-11.0 U/L). Serum b-HCG, aFP, LDH, oestradiol and inhibin levels were within the normal range. A repeated semen analysis confirmed azoospermia. Testicular ultrasound demonstrated a well-defined hypoechoic mass, measuring 31 x 23 x 17 mm and containing several flecks of calcification, arising from the lower pole of the left testis. A left orchidectomy was performed. Macroscopical histopathological examination revealed a single firm dark brown nodule 2.8 cm in diameter arising from the lower pole of the testis. The tumor distended the capsule of the testis without extending through it. Microscopical examination was consistent with a Leydig cell tumor. Computerised tomography of the chest, abdomen and pelvis was normal. Six months later, laboratory investigations revealed a serum testosterone of 14.3 nmol/l, an LH of 5.4 U/L and an FSH of 4.3 U/L, respectively. A repeated semen analysis was normal: volume 1.8 ml(2-10 ml), count 124 x 10(6) (20-350 x 10(6)), motility 80%(>60%), abnormal forms <15%(<15%). Three months later his wife was pregnant. In summary, our patient presented with azoospermia, secondary to a Leydig cell tumor, which was reversible after removal of the tumor.

Journal Article↗