The lakes of Titan.

The surface of Saturn's haze-shrouded moon Titan has long been proposed to have oceans or lakes, on the basis of the stability of liquid methane at the surface. Initial visible and radar imaging failed to find any evidence of an ocean, although abundant evidence was found that flowing liquids have existed on the surface. Here we provide definitive evidence for the presence of lakes on the surface of Titan, obtained during the Cassini Radar flyby of Titan on 22 July 2006 (T16). The radar imaging polewards of 70 degrees north shows more than 75 circular to irregular radar-dark patches, in a region where liquid methane and ethane are expected to be abundant and stable on the surface. The radar-dark patches are interpreted as lakes on the basis of their very low radar reflectivity and morphological similarities to lakes, including associated channels and location in topographic depressions. Some of the lakes do not completely fill the depressions in which they lie, and apparently dry depressions are present. We interpret this to indicate that lakes are present in a number of states, including partly dry and liquid-filled. These northern-hemisphere lakes constitute the strongest evidence yet that a condensable-liquid hydrological cycle is active in Titan's surface and atmosphere, in which the lakes are filled through rainfall and/or intersection with the subsurface 'liquid methane' table.

Titan Radar Mapper observations from Cassini's T3 fly-by.

Cassini's Titan Radar Mapper imaged the surface of Saturn's moon Titan on its February 2005 fly-by (denoted T3), collecting high-resolution synthetic-aperture radar and larger-scale radiometry and scatterometry data. These data provide the first definitive identification of impact craters on the surface of Titan, networks of fluvial channels and surficial dark streaks that may be longitudinal dunes. Here we describe this great diversity of landforms. We conclude that much of the surface thus far imaged by radar of the haze-shrouded Titan is very young, with persistent geologic activity.

On the origins of fatigue strength in crystalline metallic materials.

Metallic materials experience irreversible deformation with increasing applied stress, manifested in localized slip events that result in fatigue failure upon repeated cycling. We discerned the physical origins of fatigue strength in a large set of face-centered cubic, hexagonal close-packed, and body-centered cubic metallic materials by considering cyclic deformation processes at nanometer resolution over large volumes of individual materials at the earliest stages of cycling. We identified quantitative relations between the yield strength and the ultimate tensile strength, fatigue strength, and physical characteristics of early slip localization events. The fatigue strength of metallic alloys that deform by slip could be predicted by the amplitude of slip localization during the first cycle of loading. Our observations provide a physical basis for well-known empirical fatigue laws and enable a rapid method of predicting fatigue strength as reflected by measurement of slip localization amplitude.

Acute hemodynamic changes after rapid intravenous bolus dosing of dexmedetomidine in pediatric heart transplant patients undergoing routine cardiac catheterization.

BACKGROUND: Dexmedetomidine is a highly selective α(2)-adrenoceptor agonist with sedative, anxiolytic, and analgesic properties that has minimal effects on respiratory drive. Its sedative and hypotensive effects are mediated via central α(2A) and imidazoline type 1 receptors while activation of peripheral α(2B)-adrenoceptors result in an increase in arterial blood pressure and systemic vascular resistance. In this randomized, prospective, clinical study, we attempted to quantify the short-term hemodynamic effects resulting from a rapid i.v. bolus administration of dexmedetomidine in pediatric cardiac transplant patients. METHODS: Twelve patients, aged 10 years or younger, weighing ≤40 kg, presenting for routine surveillance of right and left heart cardiac catheterization after cardiac transplantation were enrolled. After an inhaled or i.v. induction, the tracheas were intubated and anesthesia was maintained with 1 minimum alveolar concentration of isoflurane in room air, fentanyl (1 µg/kg), and rocuronium (1 mg/kg). At the completion of the planned cardiac catheterization, 100% oxygen was administered. After recording a set of baseline values that included heart rate (HR), systolic blood pressure, diastolic blood pressure, central venous pressure, systolic pulmonary artery pressure, diastolic pulmonary artery pressure, pulmonary artery wedge pressure, and thermodilution-based cardiac output, a rapid i.v. dexmedetomidine bolus of either 0.25 or 0.5 µg/kg was administered over 5 seconds. The hemodynamic measurements were repeated at 1 minute and 5 minutes. RESULTS: There were 6 patients in each group. Investigation suggested that systolic blood pressure, diastolic blood pressure, systolic pulmonary artery pressure, diastolic pulmonary artery pressure, pulmonary artery wedge pressure, and systemic vascular resistance all increased at 1 minute after rapid i.v. bolus for both doses and decreased significantly to near baseline for both doses by 5 minutes. The transient increase in pressures was more pronounced in the systemic system than in the pulmonary system. In the systemic system, there was a larger percent increase in the diastolic pressures than the systolic pressures. Cardiac output, central venous pressure, and pulmonary vascular resistance did not change significantly. HR decreased at 1 minute for both doses and was, within the 0.5 µg/kg group, the only hemodynamic variable still changed from baseline at the 5-minute time point. CONCLUSION: Rapid i.v. bolus administration of dexmedetomidine in this small sample of children having undergone heart transplants was clinically well tolerated, although it resulted in a transient but significant increase in systemic and pulmonary pressure and a decrease in HR. In the systemic system, there is a larger percent increase in the diastolic pressures than the systolic pressures and, furthermore, these transient increases in pressures were more pronounced in the systemic system than in the pulmonary system.

Species differences in hormones: yes, it does matter.

Laboratory Animal Endocrinology. Hormonal Action, Control Mechanisms and Interactions with Drugs By David D. Woodman. Chichester, UK, Wiley, 1997, $189.95 (vii+567 pages), ISBN 0-471-97262-2.

All fiber-coupled, long-term stable timing distribution for free-electron lasers with few-femtosecond jitter.

We report recent progress made in a complete fiber-optic, high-precision, long-term stable timing distribution system for synchronization of next generation X-ray free-electron lasers. Timing jitter characterization of the master laser shows less than 170-as RMS integrated jitter for frequencies above 10 kHz, limited by the detection noise floor. Timing stabilization of a 3.5-km polarization-maintaining fiber link is successfully achieved with an RMS drift of 3.3 fs over 200 h of operation using all fiber-coupled elements. This all fiber-optic implementation will greatly reduce the complexity of optical alignment in timing distribution systems and improve the overall mechanical and timing stability of the system.

Effects of age and gender on the AII-induced stimulation of prolactin release and inositol phosphate accumulation in rat anterior pituitary cells in vitro.

The stimulatory effects of Angiotensin II (AII) on prolactin secretion and inositol phosphate accumulation were examined in dispersed anterior pituitary cells collected from young (3-4 month), mature (7-8 month) and old (18-20 month) male and female rats. Physiological doses of AII (0.01-10 nM) stimulated prolactin release from cells collected from mature female rats only. This effect was antagonized by pretreatment with Saralasin, an AII receptor antagonist. Significant accumulation of the inositol phosphates was observed in cells obtained from the mature, female donors and this increase preceded the prolactin response. Although there was a small increase in total inositol phosphate accumulation in cells obtained from the old female rats, this was transient and did not coincide with a similar increase in prolactin release. These results indicate that pituitary sensitivity to AII stimulation is related to the age and the gender of the donor animal. The physiological role of pituitary AII needs to be examined in sexually mature female animals.

Modulation of the discriminative stimulus properties of cocaine: comparison of the effects of fluoxetine with 5-HT1A and 5-HT1B receptor agonists.

The present investigation examined the ability of serotonin (5-HT) agonists to substitute for, or alter (i.e. enhance or antagonize), the discriminative stimulus properties of a moderately low dose of cocaine (5 mg/kg) utilizing a two-lever, water-reinforced FR 20 drug discrimination procedure in rats. In substitution tests, the 5-HT1A receptor partial agonists buspirone and gepirone, the 5-HT1A/B receptor agonist RU 24969 and the 5-HT1B/2C receptor agonist m-trifluoromethyl-phenylpiperazine (TFMPP) failed to substitute for the cocaine stimulus, although RU 24969 did engender a maximum of 72% cocaine-lever responding. Fluoxetine (4 mg/kg) engendered primarily saline-appropriate responding. In combination tests, a fixed dose of either fluoxetine (4 mg/kg), RU 24969 (0.5 mg/kg) or TFMPP (0.5 mg/kg) produced a leftward shift in the cocaine dose-response curve (0.313-5 mg/kg). In contrast, buspirone (2.5-20 mg/kg) resulted in a dose-dependent attenuation (approximately 60% reduction) of the cocaine stimulus. Moreover, a dose of 10 mg/kg of buspirone co-administered with various doses of cocaine (1.25-10 mg/kg) engendered a rightward shift in the cocaine dose-response curve. Gepirone in combination with cocaine neither enhanced nor antagonized the cocaine discriminative stimulus. Whereas 5-HT agonists do not fully substitute for cocaine, the present results demonstrate that 5-HT1B, but not 5-HT1A, receptor agonists can modulate the discriminative stimulus properties of cocaine in a manner similar to that observed following administration of the 5-HT reuptake inhibitor fluoxetine. The ability of buspirone, but not gepirone, to attenuate the cocaine stimulus probably reflects its dopamine (DA) D2 receptor antagonist properties and not its efficacy at 5-HT1A receptors.

Effect of water temperature on dermal exposure to chloroform.

We have developed and applied a new measurement methodology to investigate dermal absorption of chloroform while bathing. Ten subjects bathed in chlorinated water while breathing pure air through a face mask. Their exhaled breath was delivered to a glow discharge source/ion trap mass spectrometer for continuous real-time measurement of chloroform in the breath. This new method provides abundant data compared to previous discrete time-integrated breath sampling methods. The method is particularly well suited to studying dermal exposure because the full face mask eliminates exposure to contaminated air. Seven of the 10 subjects bathed in water at two or three different temperatures between 30 degrees C and 40 degrees C. Subjects at the highest temperatures exhaled about 30 times more chloroform than the same subjects at the lowest temperatures. This probably results from a decline in blood flow to the skin at the lower temperatures as the body seeks to conserve heat forcing the chloroform to diffuse over a much greater path length before encountering the blood. These results suggest that pharmacokinetic models need to employ temperature-dependent parameters. Two existing models predict quite different times of about 12 min and 29 min for chloroform flux through the stratum corneum to reach equilibrium. At 40 degrees C, the time for the flux to reach a near steady-state value is 6-9 min. Although uptake and decay processes involve several body compartments, the complicating effect of the stratum corneum lag time made it difficult to fit multiexponential curves to the data; however, a single-compartment model gave a satisfactory fit.

The role of the mu(1) opioid receptor subtype in the regulation of prolactin and growth hormone secretion by Beta-endorphin in female rats: studies with naloxonazine.

The µ opioid receptor subtype has been reported to mediate the prolactin secretory response to opioids. This receptor subtype has been implicated in the morphine-induced prolactin increase, as well as the prolactin response to µ-specific opioid peptides. Subtypes of the µ receptor have been proposed and the µ(1) , site has been postulated as the receptor subtype involved in the morphine-induced prolactin secretory response. However, the role of this receptor subtype in mediating the endocrine effects of the endogenous opioid peptides has not been characterized. In order to determine the physiological significance of this receptor subtype, animals were pretreated with saline, WIN 44,441-3 (a µ, δ and κ antagonist) or naloxonazine (a µ(1) antagonist) followed by a stimulatory dose of morphine or ß-endorphin. A dose response study for ß-endorphin was conducted to determine the minimal stimulatory dose of ß-endorphin on the prolactin and growth hormone (GH) secretory response. The dose response study indicated that ß-endorphin is a more potent stimulus for prolactin release than for GH. A dose as low as 25 ng increased prolactin levels as much as 100-fold in both lactating and diestrous female rats. In contrast, 2.5 µg ß-endorphin was required in order to consistently and significantly increase circulating levels of GH by 2- to 3-fold. WIN 44,441-3 antagonized the stimulatory effects of ß-endorphin on both prolactin and GH secretion. Naloxonazine pretreatment abolished the morphine-induced prolactin secretory response, without affecting the GH increase in diestrous females. Naloxonazine also antagonized the prolactin response to ß-endorphin in both lactating and diestrous females. In addition, it attenuated the GH secretory response but did not totally abolish it. These data indicate that ß-endorphin elicits an increase in prolactin release through an opioid specific receptor which appears to be the µ(1) opioid receptor subtype. They further suggest that ß-endorphin may increase GH levels, at least partially, via its action at this µ(1) site.

Inhibition of tuberoinfundibular dopaminergic neural activity during suckling: involvement of mu and kappa opiate receptor subtypes.

Previous studies have shown that mu (mu) and kappa (kappa) opioid antagonists inhibit suckling-induced prolactin release. Prolactin responses elicited by pup suckling or opioid administration are mediated, at least in part, by suppression of dopamine (DA) release from tuberoinfundibular dopaminergic (TIDA) neurons in the hypothalamus. We examined the effects of the mu opiate receptor antagonist, beta-funaltrexamine (beta-FNA), and the kappa opiate receptor antagonist, nor-binaltorphimine (nor-BNI) on the activity of TIDA neurons in lactating rats. TIDA neuronal activity was determined by measuring DOPA accumulation in the caudate putamen (CP) and median eminence (ME). The effects of opioid antagonist treatment were determined in pup-deprived (low circulating prolactin levels) or pup-suckled rats (high circulating prolactin levels). The accumulation of 5-hydroxytryptophan (5-HTP) in the medial preoptic area (MPOA), the anterior hypothalamus (AH) and the median eminence (ME) was quantified as an index of serotonergic activity in the same animals for comparative purposes. In vehicle treated rats, suckling caused a significant and selective decrease in DOPA accumulation in the ME. beta-FNA (5 micrograms, i.c.v.) pretreatment significantly increased DOPA accumulation in the ME of pup-deprived and pup-suckled rats. beta-FNA pretreatment also prevented the suckling-induced suppression of DOPA accumulation in the ME. In contrast to the actions of beta-FNA, pretreatment with nor-BNI (8 micrograms, i.c.v.) did not significantly affect the activity of the TIDA neurons in pup-deprived or pup-suckled rats. Suckling alone did not alter 5-HTP accumulation in any of the brain regions examined, and neither opioid antagonist had appreciable effects on 5-HTP accumulation. These results demonstrate that the EOP tonically inhibit the TIDA neurons in both pup-deprived and pup-suckled, post-partum female rats by acting through the mu, but not the kappa, opiate receptor subtype. Furthermore, the suckling-induced inhibition of TIDA neurons is also mediated through the EOP acting at mu, but not kappa opioid receptors.

Differentiation between the stimulus effects of (+)-lysergic acid diethylamide and lisuride using a three-choice, drug discrimination procedure.

The discriminative stimulus properties of (+)-lysergic acid diethylamide (LSD) and lisuride hydrogen maleate (LHM), were compared in a three-choice, water reinforced (FR 20) situation in which rats were required to press one lever following LSD (0.08 mg/kg), a second lever following LHM (0.04 mg/kg), and a third lever following saline. Reliable drug-appropriate responding was established in 72 sessions. Dose-response tests with LSD and LHM indicated that, as dose increased, the per cent of responding on the lever associated with the particular training drug also increased; little or no cross-transfer occurred between LSD and LHM. In generalization tests, the serotonin (5-HT) agonist quipazine substituted for LSD but not LHM while the dopamine (DA) agonist apomorphine mimicked LHM but not LSD; an unrelated compound, pentylenetetrazol (PTZ), produced responding on the saline-appropriate lever. In combination tests, 5-HT antagonists (e.g., BC-105 and low doses of pirenperone) blocked responding on the LSD lever while DA antagonists (e.g., haloperidol and much higher doses of pirenperone) blocked LHM-appropriate responding. These data suggest that the three-lever (D-D-N) procedure is similar to, but can be more sensitive than the two-lever (D-N) procedure (because it can differentiate between LSD and LHM); they therefore at least partially support the hypothesis that three-choice discriminations can be conceptualized as two separate, two-choice (D-N) discriminations (Jarbe and Swedberg 1982). The results also confirm suggestion that the stimulus effects of LSD and LHM are mediated by different mechanisms; the primary action of LSD is serotonergic (5-HT2), while that of LHM is dopaminergic (White 1986).

Monoamine reuptake inhibitors enhance the discriminative state induced by cocaine in the rat.

Cocaine inhibits the reuptake of dopamine (DA), norepinephrine (NE), and serotonin (5-HT). To investigate the relative role of such reuptake processes in the discriminative stimulus properties of cocaine, male rats (N = 16) were trained to discriminate cocaine (10 mg/kg) from saline in a two-lever, water-reinforced drug discrimination task and were administered neuroactive compounds during substitution or combination tests. The DA reuptake inhibitor GBR 12909 (2-16 mg/kg) completely mimicked cocaine. The reuptake inhibitors for NE (desipramine; 2-8 mg/kg) and 5-HT (fluoxetine; 0.625-5 mg/kg) did not substitute for the training drug. A low dose of either desipramine (3 mg/kg), fluoxetine (1.25 mg/kg), or GBR 12909 (2 mg/kg) coadministered with low doses of cocaine (0.625-2.5 mg/kg) enhanced the discriminative stimulus properties of this psychostimulant. The dose predicted to elicit 50% drug-lever responding is reduced (ED50) in the presence of desipramine (0.38 mg/kg), fluoxetine (0.79 mg/kg) or GBR 12909 (0.84 mg/kg) compared to the ED50 for cocaine (1.57 mg/kg) in the absence of any reuptake inhibitor. The finding that GBR 12909 mimics the cocaine cue corroborates the hypothesis that the stimulus properties of cocaine are mediated predominantly by DA systems. The potentiation of the stimulus effects of cocaine by monoamine reuptake inhibitors in rats suggests that these drugs could also amplify the subjective effects of cocaine in humans, a possibility that should be considered given the current use of antidepressants in the treatment of cocaine abusers.

Discriminative stimulus properties of the serotonin agonist MK 212.

In an attempt to clarify the role of 5-hydroxytryptamine (5-HT) in the discriminative stimulus properties of MK 212 (6-chloro-2[1-piperazinyl]pyrazine), male Sprague-Dawley rats were trained to discriminate 0.5 mg/kg of this compound from saline. While the putative 5-HT agonists fenfluramine and m-chlorophenylpiperazine (MCPP) mimicked MK 212 in a dose-related manner, d-lysergic acid diethylamide (LSD), 8-hydroxy-2(di-n-propylamino)tetralin (8-OHDPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), quipazine, Ru 24969, and 1-(m-trifluoromethylphenyl)piperazine (TFMPP) failed to substitute completely. The 5-HT1/5-HT2 antagonists BC 105, metergoline, and methysergide completely blocked the MK 212 cue, while the selective 5-HT2 antagonists ketanserin and pirenperone, the dopamine antagonists haloperidol and spiperone, and the beta-noradrenergic antagonist propranolol were without effect. The substitutions of fenfluramine and MCPP for MK 212 support a role for 5-HT in the MK 212 cue; however, the lack of substitution of many other 5-HT agonists is difficult to explain. The complete antagonism by 5-HT1/5-HT2 but not by selective 5-HT2, antagonists suggests the possibility that 5-HT1 receptors mediate the stimulus properties of MK 212. Further research is needed to support this hypothesis and to investigate the relative role of 5-HT and other neurotransmitters in the stimulus effects of MK 212.

Dopamine D1 and D2 mediation of the discriminative stimulus properties of d-amphetamine and cocaine.

Evidence suggests that stimulants such as d-amphetamine and cocaine act presynaptically by increasing the amount of dopamine (DA) available to stimulate postsynaptic DA receptors. Since two subpopulations of DA receptors (D1 and D2) exist, we investigated the role of both of these receptor subtypes in mediating the internal "state" produced by these stimulants. Two groups of rats (N = 8/group) were trained to discriminate intraperitoneal (IP) injections of either d-amphetamine (1 mg/kg) or cocaine (10 mg/kg) from saline in a two-lever, water-reinforced, drug discrimination task. After stable performance was established (i.e., more than 85% correct under each training condition), substitution and combination tests were conducted with selective D1 and D2 agonists and antagonists. The D2 agonist quinpirole (0.0313-0.125 mg/kg) mimicked both stimulant cues while the D1 agonist SKF 38393 (5-20 mg/kg) substituted partially for cocaine but not d-amphetamine. Combination tests with DA antagonists indicated that both the D1 antagonist SCH 23390 (0.0063-0.25 mg/kg) and the D2 antagonist haloperidol (0.125-0.5 mg/kg) attenuated the effects of both stimulants; in addition, the substitution of cocaine (20 mg/kg) for d-amphetamine was blocked by both DA antagonists. The ability of both D1 and D2 antagonists to attenuate the stimulus effects of d-amphetamine and cocaine raises the possibility that a synergistic ("enabling") interaction between D1 and D2 receptors may modulate stimulant cues.

Discriminative stimulus properties of cocaine: modulation by dopamine D1 receptors in the nucleus accumbens.

Dopamine (DA) D1 and D2 receptors are involved in mediating the behavioral effects of cocaine, including its discriminative stimulus properties. The purpose of the present study was to investigate the role of the nucleus accumbens and, in particular, accumbens DA D1 receptors in modulating the stimulus effects of cocaine. Thus, rats were trained to discriminate cocaine (10 mg/kg, IP) from saline using a two-lever, water-reinforced FR 20 drug discrimination task. In substitution tests, systemic (IP) administration of cocaine (0.625-20 mg/kg) produced a dose-related increase in cocaine-appropriate responding. Microinjections of cocaine (2.5-40 micrograms) into the nucleus accumbens also engendered dose-dependent and complete substitutions (> 80% drug-lever responding) for the systemic training dose of cocaine, whereas intra-accumbens artificial cerebrospinal fluid (1 microliter/side) produced primarily saline-appropriate responding. In antagonism tests, pretreatment with the DA D1 antagonist SCH 23390 (3-12 micrograms/kg) completely antagonized (< 20% drug-lever responding) a dose of cocaine (5 mg/kg) that produced greater than 90% cocaine-lever responding when given alone. Additionally, intra-accumbens injections of SCH 23390 (0.025-0.4 microgram) prior to systemic cocaine (5 mg/kg) also significantly blocked the cocaine stimulus. The present results confirm the importance of the nucleus accumbens in mediating the discriminative stimulus properties of cocaine and suggest a primary role of accumbens DA D1 receptors in modulating this behavior.

Effects of the putative dopamine autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 on the discriminative stimulus properties of cocaine.

Recent evidence suggests that the putative dopamine (DA) autoreceptor antagonists, (+)-AJ 76 and (+)-UH 232, share some neurochemical and behavioral effects with both psychostimulants and neuroleptics. The ability of (+)-AJ 76 and (+)-UH 232 to mimic or antagonize the stimulus effects of cocaine was investigated in rats trained to discriminate 5 mg/kg (N = 8) or 10 mg/kg (N = 8) of cocaine from saline in a two-lever, water-reinforced, drug discrimination task. In the cocaine (10 mg/kg) group, administration of (+)-AJ 76 (2.5-20 mg/kg) engendered only a partial substitution for cocaine (maximum 60% cocaine-lever responses). Given in combination with cocaine (10 mg/kg), (+)-AJ 76 (2.5-40 mg/kg) did not significantly attenuate the cocaine cue. A fixed dose of (+)-AJ 76 (2.5 or 10 mg/kg) plus various doses of cocaine (1.25-5 mg/kg) did not alter the cocaine dose-response curve. (+)-UH 232 (2-16 mg/kg) produced primarily saline-appropriate responding in rats trained to discriminate 5 mg/kg of cocaine and was unable to block the interoceptive cocaine state when given in combination with cocaine (5 mg/kg). (+)-UH 232 (2 or 8 mg/kg) also did not alter the cocaine dose-response curve. These results suggest that (+)-AJ 76 and (+)-UH 232 elicit only weak or no cocaine-like stimulus effects and, unlike neuroleptics, do not attenuate the cocaine cue.

The discriminative stimulus properties of cocaine: effects of microinfusion of cocaine, a 5-HT1A agonist or antagonist, into the ventral tegmental area.

Serotonin (5-HT) afferents may modulate the dopamine mesoaccumbens circuit, which has been shown to be critically involved in the locomotor stimulatory, discriminative stimulus, and rewarding properties of cocaine. In the present study, we investigated the role of 5-HT1A receptors in the ventral tegmental area (VTA) in mediating the discriminative stimulus effects of cocaine. Male Sprague-Dawley rats were trained to discriminate cocaine (10 mg/kg) from saline in a two-lever, water-reinforced FR 20 task. After acquiring the cocaine-saline discrimination, rats were stereotaxically implanted with bilateral guide cannulae into the VTA or adjacent substantia nigra reticulata (SNR). Intraperitoneal administration of cocaine (0.625-10 mg/kg) produced a dose-related increase in drug-lever responding. Both intra-VTA and intra-SNR infusion of cocaine (12.5-50 microg/0.5 microl/side) engendered primarily saline-like responding. Microinjection of the 5-HT1A agonist 8-hydroxy-2-(di-N-propylamino) tetralin (DPAT; 0.1-10 microg/0.5 microl/side) or the 5-HT1A antagonist WAY 100635 (0.01-1.0 microg/0.5 microl/side) into the VTA or SNR did not substitute for the systemic cocaine cue. Further, intra-VTA or intra-SNR DPAT or WAY 100635 in combination with systemic doses of cocaine did not alter (i.e., attenuate or potentiate) the systemic cocaine cue. Overall, these data indicate that 5-HT1A receptors in the VTA do not mediate or modulate the discriminative stimulus effects of cocaine in the rat.

Prolactin release and tuberoinfundibular dopaminergic neuronal activity following single and double injections of morphine.

It is well established that opiate agonists alter tuberoinfundibular dopaminergic activity and consequently prolactin release. The purpose of this study was to characterize the effects of morphine on prolactin secretion and tuberoinfundibular dopaminergic neuronal activity with respect to time after administration. Additionally, the effect of an initial morphine injection on the response produced by a second injection of morphine was determined. The rate of depletion of median eminence dopamine content following synthesis inhibition by alpha-methyl-p-tyrosine was used as an index of dopaminergic neuronal activity. Male rats given a single injection of morphine sulfate (15 mg/kg, s.c.) showed a significant increase in circulating prolactin levels and had a lower rate of median eminence dopamine turnover 1 h after injection. Four hours after injection, circulating prolactin levels were similar to those in vehicle treated rats, while dopamine turnover was significantly higher than controls. When two injections of morphine sulfate (15 mg/kg, s.c.) were given 4 h apart, the stimulation of prolactin release produced by the second injection was significantly attenuated. Although this second injection caused a significant decrease in dopamine turnover, the turnover rate following this injection was significantly greater than that following the initial injection. The combination of fluoxetine and 5-hydroxytryptophan (FLX/5-HTP) caused an initial increase in prolactin secretion with plasma values returning to basal levels by 4 h. When rats were pretreated with FLX/5-HTP instead of morphine, the prolactin response to an injection of morphine 4 h later was not attenuated. Similarly a FLX/5-HTP pretreatment had no influence on a second injection of FLX/5-HTP administered 4 h later.(ABSTRACT TRUNCATED AT 250 WORDS)

Orphanin FQ stimulates prolactin and growth hormone release in male and female rats.

Intracerebroventricular administration of Orphanin FQ (5.5, 55 or 550 pmol) caused a dose-related increase in prolactin secretion in both male and female rats and stimulated GH secretion in males. The magnitude of the prolactin secretory response was greater in females than in males. These effects of OFQ on prolactin and growth hormone release are the same as the stimulatory effects of the endogenous opioid peptides.