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Biomedical subjects

A D Levy

Publications and source records attributed to A D Levy.

At least 19 recordsLinked to original sources
PubMed2001

Noninvasive imaging approach to patients with suspected hepatobiliary disease.

Technologic advances in ultrasound, computed tomography (CT), and magnetic resonance imaging over the past decade have greatly improved the noninvasive evaluation of the liver and biliary tree. Each imaging modality offers unique and valuable information that aids in the evaluation of the liver and biliary tree. Improved spatial resolution, harmonic imaging, and color and power Doppler have transformed hepatobiliary ultrasound such that it is often the initial examination for many patients. Helical CT permits the characterization of the hepatic parenchyma during multiple phases of contrast enhancement. New rapid magnetic resonance sequences allow images of the liver to be obtained without motion artifact. The multiplanar techniques of magnetic resonance cholangiography allow noninvasive visualization of the biliary and pancreatic ducts. This article reviews the noninvasive imaging approach to patients with suspected hepatobiliary disease.

Biliary Tract Diseases↗
PubMed1998

A comparison of the oxytocin and vasopressin responses to the 5-HT1A agonist and potential anxiolytic drug alnespirone (S-20499).

The effect of the serotonin1A (5-HT1A) agonist alnespirone (S-20499) on the secretion of both oxytocin and vasopressin was examined in the same conscious, unrestrained male rats. The dose-response and time-course effects on the secretion of oxytocin and vasopressin revealed that alnespirone stimulated oxytocin in a dose-dependent manner, but did not increase vasopressin secretion. Time of maximal effect following injection of alnespirone (5 mg/kg, i.p.) was as early as 15 min postinjection, with significant stimulation persisting for 30 min. Pretreatment with a low dose of the 5-HT1A/beta-adrenoceptor antagonist (-)-pindolol (0.3 mg/kg, s.c.), 30 min prior to injection of alnespirone (0, 2, 5, and 10 mg/kg, i.p.) shifted the dose-response curve to the right and inhibited the effect of alnespirone on plasma oxytocin concentration. Furthermore, pretreatment with a low or a high dose of the 5-HT1A/2A/dopamine D2 antagonist spiperone (0.01 or 3 mg/kg, s.c.) dose dependently shifted the alnespirone dose-response curve effect of alnespirone to the right. None of these drugs, alone or in combination, altered plasma vasopressin levels. These studies suggest that 5-HT1A receptor mechanisms mediate the effect of alnespirone on the secretion of oxytocin. Furthermore, these studies suggest that 5-HT1A receptor mechanisms do not participate in the serotonergic regulation of vasopressin secretion.

Adrenergic beta-Antagonists↗
PubMed1996

Serotonergic regulation of renin and prolactin secretion.

Drugs that, directly or indirectly produce activation of serotonin (5-HT) receptors increase plasma concentrations of both prolactin and renin. The serotonergic regulation of prolactin and renin secretion share several common characteristics. Serotonergic neurons originating in the dorsal raphe and terminating in the hypothalamus stimulate the secretion of both prolactin and renin. Destruction of cells in the hypothalamic paraventricular nucleus (PVN) inhibits both the prolactin and renin responses to 5-HT agonists and 5-HT-releasing drugs. Activation of 5-HT2 receptors increases the secretion of both prolactin and renin, while activation of other 5-HT receptor subtypes has differential effects on these hormones. However, there are also differences between the serotonergic mechanisms that regulate the secretion of prolactin and renin. Activation of 5-HT1A receptors increases the secretion of prolactin but not of renin. In addition, activation of peripheral 5-HT2 receptors stimulates the secretion of renin, while activation of peripheral 5-HT3 receptors increases plasma levels of prolactin but not renin. In humans, the effect of 5-HT-releasing drugs and 5-HT agonists on plasma prolactin concentrations has been studied to a greater extent than effects on most other hormones. In contrast, the renin response to 5-HT agonists and 5-HT releasers has not been well characterized in humans. Because of the important role of the renin-angiotensin system in cardiovascular regulation, studies on the serotonergic regulation of renin release in humans could increase our understanding of cardiovascular disorders associated with altered serotonergic function. Examples include anxiety and consequences of cocaine abuse. In conclusion, comparing the serotonergic regulation of prolactin and renin secretion indicates similarities that might shed light on common brain mechanisms that regulate neuroendocrine function.

Animals↗
PubMed1996

Neuroendocrine pharmacology of three serotonin releasers: 1-(1,3-benzodioxol-5-yl)-2-(methylamino)butane (MBDB), 5-methoxy-6-methyl-2-aminoindan (MMAi) and p-methylthioamphetamine (MTA).

Serotonin (5-hydroxytryptamine, 5-HT)-releasing drugs are important experimental tools to examine the role of serotonergic nerve terminals in the secretion of hormones. The drugs 1-(1,3-benzodioxol-5-yl)-2-(methylamino)butane (MBDB), 5-methoxy-6-methyl-2-aminoindan (MMAI) and p-methylthioamphetamine (MTA) have been suggested to be 5-HT releasers. The present study characterized MBDB, MMAI and MTA by using their effects on the secretion of the hormones adrenal corticotrophin (ACTH), corticosterone, prolactin, oxytocin and renin. The time course of the effect of MBDB, MMAI and MTA (5 mg/kg, i.p.) showed that the peak effect on plasma ACTH occurred 10 min after the injection, whereas the prolactin response did not reach a maximum until 30 min after injection. MBDB increased plasma renin concentration within 10 min, whereas the effect of MTA was significant only at 30 min after injection. All three 5-HT releasers decreased HR (within 5 min) and blood pressure (at 15 min after injection). MBDB, MMAI and MTA increased plasma ACTH, corticosterone, prolactin and renin levels in a dose-dependent manner, whereas no changes were observed in plasma vasopressin concentrations. MTA and MMAI, but not MBDB, significantly increased plasma oxytocin concentrations in a dose-dependent manner. Pretreatment of rats with fluoxetine blocked the ACTH response to MBDB and MMAI, but not to MTA. The prolactin response to all three 5-HT releasers was blocked by fluoxetine. The oxytocin response to MTA and MMAI was inhibited by fluoxetine. The renin responses to all three 5-HT releasers were not significantly inhibited by fluoxetine. The results suggest that MBDB, MMAI and MTA can increase the secretion of several hormones, at least in part, through stimulation of serotonergic neurotransmission. However, these three 5-HT releasers seem to have effects on other (and as yet uncharacterized) mechanisms that can stimulate the secretion of some hormones.

3,4-Methylenedioxyamphetamine↗
PubMed1995

Neuroendocrine profile of the potential anxiolytic drug S-20499.

The neuroendocrine profile of the serotonin 5-HT1A receptor agonist and potential anxiolytic drug (+)-4[N-(5-methoxy-chroman-3-yl)N-propylamino]butyl-8-azaspiro-(4, 5)-decane - 7,9-dione (S-20499) was examined in conscious male rats. S-20499 (0.01-20 mg/kg i.p.) dose-dependently elevated plasma adrenocorticotropin (ACTH) and corticosterone concentrations, with maximal effects observed at 15-30 and 30-60 min respectively. S-20499 also reduced plasma prolactin concentration, and did not alter plasma renin activity. S-20499 (1 mg/kg i.p.) also reduced blood pressure and heart rate within 10 min, suggesting reduced sympathetic output. Pretreatment with the 5-HT1A receptor antagonists (-)-pindolol (0.3 mg/kg i.p.) or spiperone (0.01 or 3 mg/kg s.c.) significantly attenuated the stimulatory effects of S-20499 on plasma ACTH and/or corticosterone concentrations. The data suggest that S-20499 stimulates the hypothalamic-pituitary adrenal axis by activating 5-HT1A receptors, although activation of dopamine D2 receptors may contribute to these responses. Like other 5-HT1A receptor agonists, S-20499 does not increase renin secretion. Additionally, it reduces prolactin secretion, presumably by acting as a weak dopamine D2 receptor agonist in the pituitary.

Adrenocorticotropic Hormone↗
PubMed1995

Hypothalamic paraventricular, but not supraoptic neurons, mediate the serotonergic stimulation of oxytocin secretion.

The purpose of the present studies was to determine whether cells in the hypothalamic paraventricular (PVN) or supraoptic (SON) nuclei mediate the serotonergic stimulation of oxytocin secretion. The serotonergic stimulus consisted of injection of the 5-HT-releasing drug p-chloroamphetamine (8 mg/kg, IP). The validity of this approach was verified by comparing this drug with another 5-HT releaser, d-fenfluramine (5 mg/kg, IP). Both 5-HT releasers increased plasma oxytocin concentration. Furthermore, the 5-HT uptake blocker fluoxetine (10 mg/kg, IP) blocked the effects of both p-chloroamphetamine and d-fenfluramine on plasma oxytocin concentrations, suggesting that both 5-HT releasers must be taken up through the 5-HT transporter into 5-HT nerve terminals to increase oxytocin secretion. In the lesion experiments, cells in the hypothalamic PVN or SON were destroyed by injection of the cell-selective neurotoxin ibotenic acid. The PVN lesions reduced basal levels and inhibited the effect of p-chloroamphetamine (8 mg/kg, IP) on plasma oxytocin concentration. In contrast, SON lesions did not alter basal oxytocin levels and did not reduce the oxytocin response to p-chloroamphetamine, suggesting that the SON is not involved in the serotonergic stimulation of oxytocin secretion. Site specificity of the PVN lesions was confirmed when injections of ibotenic acid into the hypothalamic dorsomedial nucleus (DMN), immediately caudal to the PVN, potentiated the oxytocin response to p-chloroamphetamine, suggesting that the DMN exerts an inhibitory influence on the secretion of oxytocin. Taken together, the data suggest that the serotonergic stimulation of oxytocin secretion involves PVN, but not SON, oxytocin neurons.

Animals↗
PubMed1994

Attenuation of hormone responses to the 5-HT1A agonist ipsapirone by long-term treatment with fluoxetine, but not desipramine, in male rats.

The present study had two objectives: (1) to provide information on neuroendocrine challenge tests that can lead to diagnostic tests in humans; and (2) to confirm our previous observation that chronic fluoxetine selectively inhibits serotonin (5-HT1A) receptor function. We determined the effect of chronic fluoxetine and desipramine (DMI) on the hormone response to ipsapirone, a 5-HT1A agonist and a potential anxiolytic drug. Ipsapirone increased oxytocin, adrenocorticotropic hormone (ACTH), corticosterone, and prolactin, but not renin or vasopressin concentrations in plasma. Chronic fluoxetine, but not DMI, significantly inhibited the effect of ipsapirone on plasma oxytocin, ACTH and corticosterone concentrations. Chronic fluoxetine also reduced the Bmax for 3H-8-hydroxy-2-(dipropylamino) tetralin (3H-8-OH-DPAT) labelled 5-HT1A receptors in the midbrain. Neither antidepressant altered the density or affinity of 5-HT uptake sites. In conclusion, the present results confirm our previous results using 8-OH-DPAT as a challenge, and suggest that chronic 5-HT uptake inhibition results in adaptive changes leading to decreased function of the 5-HT1A receptor system. Finally, because ipsapirone may be administered to humans, it might be usable to evaluate 5-HT1A receptor function in depressed patients.

Adrenocorticotropic Hormone↗
PubMed1994

Monoaminergic regulation of neuroendocrine function and its modification by cocaine.

Neuroendocrine pharmacology represents a potentially valuable approach to the assessment of alterations in neuronal function in the brain of human cocaine abusers. Neuroendocrine effects of the monoamine uptake inhibitor cocaine have predominantly been examined in laboratory animals. These preclinical studies may help to identify the optimal challenge tests to be performed in clinical studies. In laboratory animals, acute administration of cocaine activates the hypothalamic-pituitary-adrenal axis, via actions on serotonergic and dopaminergic neurons in the brain. Cocaine also reduces prolactin secretion, probably by dopaminergic mechanisms, although the necessary studies to confirm this hypothesis have not been performed. Cocaine also reduces renin secretion, and increases vasopressin and luteinizing hormone secretion, by mechanisms which have not been clearly established. The adrenocorticotropin, corticosterone, prolactin, and renin responses to cocaine are generally unaltered by prior cocaine exposure, suggesting that tolerance or sensitization to the endocrine effects of cocaine does not occur. However, several studies have determined that prior cocaine exposure alters the serotonergic regulation of hormone secretion. Chronic cocaine exposure reduces some of the hormone responses to the serotonin (5-HT) releasers p-chloroamphetamine and d-fenfluramine, suggesting deficits in the functional status of serotonergic nerve terminals. Additionally, repeated cocaine exposure produces subsensitive 5-HT1A-mediated hormone responses, and supersensitive 5-HT2-mediated responses. Alterations in dopaminergic- or noradrenergic-mediated hormone responses have not been examined in animals chronically exposed to cocaine. Endocrine studies in human cocaine abusers have largely examined basal hormone levels or the hormone responses to cocaine. Strong conclusions from these studies are limited because (1) many neuronal and nonneuronal systems regulate secretion of each hormone, so that alterations in basal hormone levels cannot be attributed to only one neurotransmitter; and (2) hormone responses to cocaine cannot be examined in cocaine-naive subjects due to ethical considerations, making it impossible to determine whether the response in cocaine abusers is abnormal. It may be more beneficial for studies in cocaine abusers to examine the hormone responses to drugs that specifically affect monoaminergic neurons and compare the data with cocaine-naive individuals.

Animals↗
PubMed1994

Influence of repeated cocaine exposure on the endocrine and behavioral responses to stress in rats.

Previous studies have determined that chronic cocaine exposure inhibits the serotonergic stimulation of hormone secretion. The present experiments were conducted to determine whether the endocrine responses to stress could be a useful approach to assess the influence of cocaine exposure on neuronal function. Male rats received twice daily injections of cocaine (1-15 mg/kg, IP) for 7 days. Animals were subsequently exposed to different stressors, i.e. conditioned emotional stress utilizing a low (0.5 mA) or high (1.5 mA) intensity footshock during training, or to immobilization stress. Immediately after the stress procedures, blood samples were collected for radioimmunoassay of plasma corticosterone, prolactin, and renin concentrations. Repeated cocaine exposure attenuated the stress-induced elevations of corticosterone and prolactin secretion, and attenuated some of the behavioral effects of the low intensity conditioned emotional stress. When exposed to the high intensity conditioned emotional stress, cocaine did not alter the endocrine or behavioral effects of stress. Finally, repeated cocaine exposure modified the immobilization stress-induced elevation of renin secretion; low doses of cocaine (1 or 5 mg/kg) attenuated, while higher doses (10 mg/kg) potentiated the renin response to immobilization stress. Thus, the influence of repeated cocaine exposure on the endocrine and behavioral responses to stress appears to depend upon the type and intensity of the stressor. Compared with previous studies which found altered neuroendocrine responses to serotonin releasers and agonists following cocaine exposure, the hormonal responses to stress are less consistently modified by cocaine.

Animals↗
PubMed1994

ICV injection of the serotonin 5-HT1B agonist CP-93,129 increases the secretion of ACTH, prolactin, and renin and increases blood pressure by nonserotonergic mechanisms.

This study tested whether a new serotonin (5-HT1B) agonist, 3-(1,2,5,6-tetrahydro-4-pyridyl)-5-propoxy-pyrrolo[3,2-b]pyridine (CP-93,129), could be used to study the potential role of 5-HT1B receptors in the secretion of adrenocorticotropic hormone (ACTH), prolactin, and renin. CP-93,129 has a high affinity for 5-HT1B receptors but low affinity for other 5-HT receptor subtypes. In addition, CP-93,129 does not readily cross the blood-brain barrier. The secretion of ACTH, prolactin, and renin is known to be increased after activation of 5-HT receptors. ICV injections of CP-93,129 (100 micrograms/kg) increased the plasma concentrations of ACTH, prolactin, and renin. CP-93,129 also increased blood pressure and reduced heart rate. To determine whether these effects of CP-93,129 are centrally mediated, we compared them with IP injection of the same dose of CP-93,129. IP-injected CP-93,129 did not alter blood pressure or heart rate and did not elevate plasma prolactin and renin concentrations. To determine whether 5-HT1B receptors mediate the central effects of CP-93,129, rats were pretreated with the 5-HT antagonists l-propranolol or metergoline prior to ICV injections of doses of CP-93,129 (0-100 micrograms/kg). The 5-HT1A/1B/2A/2C antagonist metergoline (0.5 mg/kg, IP) failed to inhibit the CP-93,129-induced elevation of ACTH, prolactin, or renin concentrations. In contrast, the 5-HT1A/1B/beta antagonist l-propranolol (20 micrograms/kg, ICV) inhibited the renin but not the ACTH or prolactin responses to ICV CP-93,129.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1994

Cocaine-induced deficits in ACTH and corticosterone responses in female rat progeny.

The objective of this study was to determine whether prenatal exposure to cocaine could produce functional changes in central serotonergic systems mediating neuroendocrine responses in female progeny. Pregnant rats were administered either saline or (-) cocaine (15 mg/kg, SC, b.i.d.) from gestational day 13-20. Progeny were fostered to nontreated lactating dams at birth. Central serotonergic function was determined by the ability of a serotonin releaser, p-chloroamphetamine (PCA), to stimulate plasma adrenocorticotropin (ACTH), corticosterone, and renin secretion in female progeny at postnatal day (PD) 30. Prenatal cocaine did not alter basal levels of ACTH, corticosterone, or renin. In contrast, ACTH and corticosterone responses to the 5-HT releaser PCA were significantly attenuated (-28% to 43%) in cocaine progeny, while the renin response to PCA was unaffected. These data suggest that cocaine administration during pregnancy can produce long-term selective alterations in neuroendocrine responses mediated by central serotonergic systems in prepubescent female progeny.

Adrenocorticotropic Hormone↗
PubMed1994

Central stimulation of renin secretion through serotonergic, noncardiovascular mechanisms.

The aims of the study were to determine; (1) whether activation of serotonin (5-HT) receptors in the brain increases renin secretion, and (2) whether the hypertensive effects of a 5-HT agonist and 5-HT releaser obscure their ability to stimulate renin release. Various drugs that increase serotonergic neuro-transmission can activate the secretion of renin from the kidneys. Many of these drugs can also elevate blood pressure. Changes in blood pressure can alter renin secretion by activating renal baroreceptor mechanisms, so that a decrease in perfusion pressure will increase renin secretion and vice versa. To address the first objective, the 5-HT agonist RU 24969 (0, 10, 100 and 200 micrograms/kg) and the 5-HT releaser p-chloroamphetamine (0, 50, 500 and 1,000 micrograms/kg) were injected intracerebroventricularly (ICV) at doses lower than those that are peripherally effective. ICV injection of RU 24969 dose-dependently increased plasma levels of renin. ICV injection of the 5-HT2A/5-HT2C antagonist LY53857 (50 micrograms/kg) inhibited the renin response to peripherally injected RU 24969 (0, 1, 5 and 10 mg/kg i.p.), suggesting that 5-HT2A/5-HT2C receptors in the brain mediate the effect of peripherally injected RU 24969 on renin secretion. In contrast, ICV injection of p-chloroamphetamine decreased renin secretion. To determine whether hypertensive actions could account for the differences between RU 24969 and p-chloroamphetamine, we measured the effects of both p-chloroamphetamine and RU 24969 on blood pressure and heart rate. ICV injection of p-chloroamphetamine (1,000 micrograms/kg) produced a large rise of 44 mm Hg at 2 min and 25 mm Hg at 5 min after injection, while ICV injection of RU 24969 (200 micrograms/kg) caused a slower and smaller blood pressure elevation of 18 mm Hg at 5 min after injection. To determine whether the hypertensive effects of both RU 24969 and p-chloroamphetamine could mask their effects on renin secretion, rats were pretreated with the alpha 1 antagonist prazosin. Administration of prazosin (1 mg/kg s.c.), which prevents the hypertensive effects of p-chloroamphetamine, exposed a stimulatory effect of ICV-injected p-chloroamphetamine (500 micrograms/kg) on renin secretion and potentiated the effect of RU 24969 (5 mg/kg i.p.) on renin release. In conclusion, these data suggest that both RU 24969 and p-chloroamphetamine increase renin secretion through central 5-HT receptors, and that these effects are partially obscured by their hypertensive actions.

Animals↗
PubMed1994

Evidence that ACTH secretion is regulated by serotonin2A/2C (5-HT2A/2C) receptors.

The present study characterized the serotonin (5-HT) receptor subtypes mediating adrenal corticotropic hormone (ACTH) and corticosterone responses to 5-HT agonists in conscious rats. The 5-HT2A/5-HT2C agonist (+/-(-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HC1 (DOI) increased plasma ACTH and corticosterone in a dose-dependent manner. The 5-HT2A/5-HT2C antagonist ritanserin (0.01 and 0.1 mg/kg sc) inhibited the DOI-induced increase in plasma ACTH, but not corticosterone. Low doses of spiperone (0.01 and 0.1 mg/kg sc) significantly reduced the ACTH response to DOI. Because spiperone has a higher affinity for 5-HT2A than 5-HT2C receptors, these data suggest that DOI stimulates ACTH secretion through 5-HT2A receptors. 5-methoxy-3-[1,2,3,4-tetrahydro-4-pyridinyl]-1H-indole (RU 24969) is a potent 5-HT1A/1B and moderate 5-HT2C agonist that also has been suggested to release 5-HT. However, p-chlorophenylalanine (PCPA) did not reduce the effect of RU 24969 on plasma ACTH, suggesting that RU 24969 only acts as a direct agonist. 6-methyl-1-[1-methylethyl]ergoline-8-carboxylic acid (LY53857) injected into the lateral cerebral ventricles (i.c.v.) inhibited the ACTH, but not corticosterone response to peripheral injection of RU 24969, suggesting that central 5-HT2A/2C receptors mediate the ACTH response. LY53857 injection (i.c.v.) also inhibited the effect of p-chloroamphetamine (i.c.v.) on plasma ACTH. However, the corticosterone response was not inhibited by LY53857, suggesting a distinct location of 5-HT receptors regulating corticosterone secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1993

Identification, sequence and expression patterns of the Caenorhabditis elegans col-36 and col-40 collagen-encoding genes.

The collagen (Col)-encoding gene family in the nematode, Caenorhabditis elegans, consists of 50-150 members. We have undertaken studies of these genes as part of the analysis of the assembly of the cuticle, the nematode's exoskeleton. We present here the complete nucleotide and deduced amino acid sequences of the col-36 and col-40 genes, both located on chromosome II and encoding cuticle Col. Both Col possess the structural properties found in the type of Col that form the cuticle, such as short Gly-Xaa-Yaa interruptions and Cys clusters at conserved sites. On the basis of identical patterns of conserved cysteines, col-36 and col-40 belong to the col-6 cuticle Col family. Semi-quantitative analysis using reverse transcription-PCR demonstrates that the col-36 transcript is present in L1 larvae and at the L1-L2 and L2d-dauer molts. The col-40 transcript is present in L1 larvae and at the L2d-dauer molt. Different members of the col-6 family are structurally related, but have different developmental expression patterns.

Amino Acid Sequence↗
PubMed1993

Long-term fluoxetine, but not desipramine, inhibits the ACTH and oxytocin responses to the 5-HT1A agonist, 8-OH-DPAT, in male rats.

The present studies determined whether serotonin 5-HT1A receptor-mediated function is modified by chronic exposure to antidepressants. Hormone responses to the 5-HT1A agonist, 8-OH-DPAT, were evaluated after long-term exposure to two antidepressants, the 5-HT uptake blocker, fluoxetine, and the norepinephrine uptake blocker, desipramine (DMI). In addition, the density and affinity of 5-HT1A receptors in the hypothalamus and cerebral cortex were measured. Male rats received fluoxetine (10 mg/kg i.p.), DMI (5 mg/kg i.p.) or saline injections once daily for 21 days. 8-OH-DPAT (0-500 micrograms/kg s.c.) was administered 18 h after the final antidepressant injection and 15 min before sacrifice. 8-OH-DPAT significantly increased plasma ACTH, corticosterone, oxytocin and prolactin, but not renin or vasopressin concentrations. Chronic injections of fluoxetine inhibited the ACTH, corticosterone and oxytocin responses to 8-OH-DPAT, suggesting reduced 5-HT1A receptor function. In contrast, chronic DMI did not alter the hormone responses to 8-OH-DPAT. The density and affinity of 5-HT1A receptors in the frontal cortex or hypothalamus were not altered by either fluoxetine or DMI. To verify that the observed effects require prolonged exposure to fluoxetine, rats received a single injection of fluoxetine (10 mg/kg, i.p.), 3 h before 8-OH-DPAT (0-500 micrograms/kg s.c.). Acute fluoxetine did not reduce any of the hormone responses to 8-OH-DPAT. In conclusion, the results suggest that chronic, but not acute, exposure to fluoxetine decreases 5-HT1A receptor function. This effect is not seen in rats chronically exposed to DMI.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Repeated exposure to cocaine produces long-lasting deficits in the serotonergic stimulation of prolactin and renin, but not adrenocorticotropin secretion.

To determine whether cocaine-induced deficits in serotonergic function are long-lasting, the neuroendocrine responses to the serotonin (5-hydroxytryptamine, 5-HT) releaser, p-chloroamphetamine were evaluated 1-8 weeks subsequent to 7 days of cocaine exposure (15 mg/kg b.i.d.). In cocaine-pretreated rats, the p-chloroamphetamine-induced elevations of prolactin and renin secretion were significantly reduced for 8 and 4 weeks, respectively. In contrast, the p-chloroamphetamine-induced elevation of adrenocorticotropic hormone (ACTH) secretion was at control values 1 week after cocaine exposure. The data suggest that some cocaine-induced deficits in serotonergic function are long-lasting.

Adrenocorticotropic Hormone↗
PubMed1993

Prenatal cocaine produces deficits in serotonin mediated neuroendocrine responses in adult rat progeny: evidence for long-term functional alterations in brain serotonin pathways.

Cocaine produces biochemical alterations in brain serotonin (5-HT) neurons. Since 5-HT is critical to the development of fetal 5-HT neurons and target tissues, we hypothesized that in utero exposure to cocaine could result in long-term alterations in postnatal 5-HT systems. Pregnant Sprague-Dawley rats were administered either saline or (-)cocaine (15 mg/kg, s.c., b.i.d.) from gestational day 13 to 20. Prenatal cocaine exposure did not alter litter size, gender number, or progeny birth weights. Functional alterations in serotonergic systems were determined in postnatal day (PD) 70 male progeny by measuring changes in 5-HT mediated plasma hormones following a single 8 mg/kg injection of the 5-HT releaser p-chloroamphetamine (PCA). Cocaine exposed male progeny exhibited significant reductions in adrenocorticotropic hormone (ACTH, -43%) and renin (-62%) responses to PCA. However, no alterations were observed in the corticosterone or prolactin response to PCA. In utero exposure to cocaine did not alter basal levels of ACTH, renin, corticosterone, or prolactin. There were no significant differences in the density of either hypothalamic or cortical 5-HT uptake sites. Likewise, there were no significant differences in the densities of any of the 5-HT1 receptor subtypes or in the density of 5-HT2 receptors in cortex. These data, which provide the first demonstration of deficits in 5-HT mediated neuroendocrine function in adult progeny following in utero exposure to cocaine, indicate long-term functional alterations of brain 5-HT systems.

Adrenocorticotropic Hormone↗