Search PubMed⌕ Search

Biomedical subjects

V D Ramirez

Publications and source records attributed to V D Ramirez.

At least 73 records · Page 4Linked to original sources

Effect of pulsatile infusion of progesterone on the in vivo activity of the luteinizing hormone-releasing hormone neural apparatus of awake unrestrained female and male rabbits.

Eight female and eight male New Zealand White rabbits were outfitted with push-pull cannulae aimed at the tuberal region of the hypothalamus and were used in 19 perfusion experiments. Animals were treated under 2 conditions: a control condition in which female (n = 4) and male (n = 4) rabbits were perfused only with artificial medium for 5-9 h, and an experimental condition in which female (n = 4) and male (n = 5) rabbits were subjected to perfusion with artificial medium, followed by 6 pulses of progesterone (P4) (10 min on, 30 min off; 10 ng/ml) during a 240-min period. Two female rabbits were also subjected to perfusion with artificial medium, followed by 6 pulses of cholesterol (10 min on, 30 min off; 10 ng/ml) during a 240-min period. The LHRH concentration in perfusates collected every 10 min was measured by RIA. In the 4 females undergoing 6- to 7-h control push-pull perfusions, spontaneous pulses were observed, with about 1 pulse every 60 min, and a variable amplitude of the LHRH signal, with a mean release of about 0.91 pg/10 min. In the 4 does treated with pulsatile P4 at 10 ng/ml, the mean LHRH release rate increased significantly from 0.91 +/- 0.13 to 1.66 +/- 0.20 pg/10 min (P less than 0.035), primarily due to an increase in the amplitude of the LHRH pulses, which were significantly greater than controls. This response occurred with an apparent mean latency of about 50 min. Cholesterol pulses did not affect the spontaneous activity of the LHRH neural apparatus. In the 4 males undergoing 5- to 9-h control push-pull perfusions, spontaneous LHRH pulses were observed with about 1 pulse every 60 min, and the mean release increased from 1.25 +/- 0.56 to 1.54 +/- 0.55 (P less than 0.035, by Wilcoxon's matched pairs signed rank test) in the late afternoon primarily due to an increase in the amplitude of the pulses. P4 pulses did not affect the spontaneous activity of the LHRH neural apparatus compared to that in the control animals. Overall, these results clearly demonstrate that although spontaneous pulsatile LHRH release from the hypothalamus of awake unrestrained female and male rabbits is similar, pulses of P4 can activate only the female LHRH neural apparatus, with an apparent latency to peak LHRH release of approximately 50 min. In addition, there appears to be an increase in LHRH mean release levels in the late afternoon to early evening in male rabbits.

Anestrus↗

In vivo neurotransmitter levels in the anterior pituitary of freely behaving intact and castrated male rats determined with push-pull perfusion and high pressure liquid chromatography coupled with electrochemical detection.

Push-pull cannulae were implanted into the anterior pituitary lobes of intact and castrated male rats, and perfusate samples were assayed for neurotransmitter concentrations with HPLC coupled with electrochemical detection. Epinephrine, which was not obtained in any of the five intact males, was detectable in three of five castrated male rats. Norepinephrine rose from nondetectable to high levels after castration in all animals. In contrast to dopamine, which was significantly decreased in castrated males, levels of 3,4-dihydrophenylacetic acid and 5-hydroxyindolacetic acid were significantly increased in castrated vs. intact male rats. Homovanillic acid was rarely detected in either intact or castrated males. These results demonstrate that the push-pull perfusion technique can be used to measure neurotransmitter levels in the anterior pituitary lobes of living rats. More importantly, after castration a distinct rise in norepinephrine and epinephrine accompanied by a decrease in dopamine was clearly detected, suggesting that these neurotransmitters may play an important role directly at the pituitary.

3,4-Dihydroxyphenylacetic Acid↗

Simultaneous measurement of gonadotropin-releasing hormone, luteinizing hormone, and follicle-stimulating hormone in the orchidectomized rat.

In the present study two recently developed techniques have been combined to enable the simultaneous in vivo determination of pulsatile release of GnRH, LH, and FSH in the orchidectomized rat. The first of these techniques involves the implantation of two vascular catheters and collecting serial blood samples through one while simultaneously infusing a replacement blood mixture through the other; consequently, blood samples can be collected for an extended period of time, and detailed plasma LH and FSH release profiles can be established for individual animals. The second technique involves push-pull perfusion of the pituitary gland to determine changes in GnRH concentration as might be perceived by the gonadotropes. For each animal (n = 6), blood (150 microliters) and push-pull perfusate (200 microliters) samples were collected at 5- and 10-min intervals, respectively, for approximately 6 h, and the hormone release profiles were determined by RIA. All of the rats showed a clear pulsatile release pattern for GnRH, LH, and FSH. Moreover, the interpulse interval was remarkably similar for each of these hormones (36.9, 41.5, and 43.5 min, respectively, as determined by PULSAR). The percentage of GnRH pulses associated with a gonadotropin pulse was 72% for LH and 76% for FSH; only 14% of the pulses were silent for both gonadotropins. These results demonstrate that in the orchidectomized rat the pulsatile pattern of GnRH release is reflected in the pulsatile pattern of not only LH but also FSH. They may, therefore, be construed to support the concept that the pulsatile secretion of both gonadotropins is primarily orchestrated by a single hypothalamic releasing hormone. Alternatively, if two separate hypothalamic releasing hormones do indeed exist (LHRH and FSH-releasing hormone), it would appear that in the orchidectomized rat their episodic release is tightly coupled to the same hypothalamic pulse generator.

Animals↗

Pregnanolone, a metabolite of progesterone, stimulates LH-RH release: in vitro and in vivo studies.

The effect of 5 beta- and 5 alpha-reduced progestins on luteinizing hormone-releasing hormone (LH-RH) release was examined using either an in vitro superfusion or an in vivo push-pull perfusion (PPP) technique. Ovariectomized rats (at least 6 days post operation: OVX) were implanted subcutaneously in the neck region with a silastic capsule containing 17 beta-estradiol (235 micrograms/ml: E2). Two days afterwards, these OVX + E2 rats were subjected to experimental conditions. Pregnanolone(5 beta-pregnane-3 beta-ol-20-one) at a low concentration of 0.01 ng/ml and an apparent latency of 1 h stimulated in vitro LH-RH release from superfused hypothalamic fragments containing the preoptic-anterior hypothalamic-mediobasal hypothalamic area (POA-AHA-MBH). The stimulatory effect of pregnanolone required estrogen-priming and a pulsatile mode of administration. In addition, the effect appeared quite specific since other closely related steroids such as epipregnanolone, R-5020 and 5 alpha-DHP were ineffective. In OVX + E2 rats bearing a push-pull cannula (PPC) in the hypothalamic area, in vivo infusion of repetitive pulses of pregnanolone through the PPC was also effective, confirming in vivo the stimulatory effect of pregnanolone on LH-RH release obtained from in vitro preparations. In these experiments, the same OVX + E2 rats served both as an experimental animal receiving pulses of pregnanolone and as a control subject when perfused only with medium after a week interval. The basal release rate of LH-RH and the response to pulsatile pregnanolone were variable among animals apparently due to different locations of PPC in the hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In vivo release of dopamine and its metabolites following a direct infusion of L-dopa into the caudate nucleus of awake, freely behaving rats using a push-pull cannula.

In vivo release of dopamine (DA) and its metabolites were determined following a direct infusion of 3,4-dihydroxyphenylalanine (L-DOPA) through a push-pull cannula in the caudate nucleus of unanesthetized, freely behaving rats. L-DOPA infusions increased the release of DA and dihydroxyphenylacetic acid (DOPAC) beginning with 10(-5) M L-DOPA, while homovanillic acid (HVA) was released consistently only following 10(-3) M L-DOPA. Maximal release of DA preceded that of DOPAC which preceded that of HVA. No salient changes in 5-hydroxyindoleacetic acid or behavior were observed following any L-DOPA dose.

3,4-Dihydroxyphenylacetic Acid↗

Effects on dopamine metabolism of MPTP and MPP+ infused through a push-pull cannula into the caudate nucleus of awake adult male rats.

Our previous data demonstrated that both 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ion (MPP+) exerted potent inhibition on endogenous 3,4-dihydroxyphenylacetic acid (DOPAC) output and potent stimulation on endogenous dopamine (DA) release from the rat corpus striatum superfused in vitro. In this report, using a push-pull perfusion technique, we examined in vivo the acute effects of MPTP and MPP+ on DA metabolism in the rat caudate nucleus (CN). MPTP or MPP+ in modified Krebs-Ringer phosphate buffer at concentrations of 10(-6), 10(-5) and 10(-4) M was administered directly into the CN for 15 min, each 90 min apart. Thirty minutes after the infusion of 10(-6) M MPP+, DOPAC output was reduced to a significantly lower value and subsequent infusions of high concentrations of MPP+ further decreased DOPAC output. Homovanillic acid (HVA) output was also decreased by MPP+ infusions, however, at higher concentrations. In respect to DA release, 1 of 10, 4 of 10 and 7 of 10 animals responded with significant increases to 10(-6), 10(-5) and 10(-4) M MPP+, respectively. On the other hand, MPTP was effective in reducing DOPAC output only at 10(-4) M and ineffective in altering DA and HVA output at all doses tested. In addition, neither drugs had a significant effect on 5-hydroxyindoleacetic acid. Accompanying the dramatic changes in DA metabolism caused by MPP+, two uncommon behavioral syndromes were also observed; tremor-body twist and body shaking.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Intermittent infusion of progesterone potentiates whereas continuous infusion reduces amphetamine-stimulated dopamine release from ovariectomized estrogen-primed rat striatal fragments superfused in vitro.

In the present experiment we examined the effect of a direct in vitro infusion of progesterone upon spontaneous and amphetamine-stimulated in vitro dopamine (DA) release and post-superfusion DA tissue concentration of corpus striatum tissue fragments from ovariectomized and estrogen-treated female rats. An intermittent infusion of progesterone at a dose of 2 ng/ml produced a significant increase in amphetamine-stimulated DA release and post-superfusion DA tissue concentration compared to similar superfusions infused with medium alone or cholesterol (2 ng/ml). Higher (50 ng/ml) or lower (0.2 ng/ml) doses of progesterone were ineffective and a continuous infusion of progesterone at an identical total concentration to that of the intermittent 2 ng/ml dose inhibited both amphetamine-stimulated DA release and post-superfusion DA tissue concentration. With the exception of 5 alpha DHP (dihydroxyprogesterone) intermittent infusions of various metabolites, a synthetic progestin (R5020) at 2 ng/ml and estradiol at both 0.2 ng/ml and 2 ng/ml failed to modify significantly the amphetamine-stimulated DA response. However, pregnanolone, 5 alpha DHP, R5020 at 2 ng/ml and estradiol at 0.2 ng/ml increased post-superfusion DA tissue concentration to levels comparable to that of progesterone. These results demonstrate that in vitro progesterone can directly alter the amphetamine-stimulated DA release from dopaminergic terminals of corpus striatal tissue fragments. This effect appears quite specific for progesterone as well as for a specific dose and mode of infusion of this gonadal steroid. Moreover, progesterone can exert opposite effects upon the amphetamine-evoked DA release from the corpus striatum as a function of its mode of infusion suggesting a means by which one hormone can differentially alter central nervous system function.

Animals↗

Is progesterone a pre-hormone in the CNS?

In this paper, experimental evidences have been presented indicating that progesterone per se appears to be a powerful modulatory steroid of presynaptic striatal dopaminergic terminals of the central nervous system of the rat. This effect of the progesterone signal is concentration as well as infusion mode dependent. Low pulsatile doses of the steroid positively modulate the mechanism by which dopamine terminals respond to amphetamine stimulation and increase tissue dopamine concentration. Whereas, continuous and/or high doses of this steroid negatively modulate the response of the dopamine terminals to amphetamine stimulation and decreases tissue dopamine concentration. This effects occurs through a membrane mediated mechanism either upon the dopamine neuron directly and/or upon an interneuron. Pregnanolone a 5- beta-3 beta-metabolite of progesterone known to activate the hypothalamic LHRH neural apparatus at the level of the hypothalamus of ovariectomized estrogen primed rats in both in vitro as well as in vivo preparations was completely ineffective at the level of the corpus striatum of similar animal preparations. Therefore, it is reasonable to assume that site specific mechanisms exist within the central nervous system which may control differentially the final action of progesterone. In the hypothalamus, pregnanolone appears to be the final signal for its action on the LHRH neural apparatus, whereas in the corpus striatum, the steroid per se, and dependent on the modality and/or the strength of the signal can either directly or indirectly up-regulate (stimulatory component) or down-regulate (inhibitory component) the activity of striatal dopaminergic terminals.

Amphetamines↗

Release of luteinizing hormone-releasing hormone (LHRH) and neuroactive substances in unanesthetized animals as estimated with push-pull cannulae (PPC).

In this report, we have reviewed recent information gathered by probing with a push-pull cannula (PPC) the in vivo activity of the suprachiasmatic nucleus (SCN), hypothalamus, and anterior pituitary gland of freely moving animals. In male and female rats, probing of the SCN with the PPC revealed distinct oscillatory patterns of 5-hydroxy indole-acetic acid (5-HIAA) output very much dependent on the position of the cannula. In males, it was also possible to demonstrate, for the first time, in vivo output of immunoreactive vasopressin (VP) most likely from the SCN. Interestingly, the output of VP was stimulated by local activation of probable 5-hydroxytryptamine (5-HT) terminals with 5-hydroxytryptophan (5-HTP), a precursor of 5-HT synthesis. Probing the hypothalamus of rats and rabbits revealed that the in vivo release of luteinizing hormone-releasing hormone (LHRH) (frequency and amplitude of the LHRH signal) can be altered by administration of estrogen to ovariectomized rats; in both species, progesterone stimulated the amplitude of the LHRH signal, but only when this steroid was infused in pulses--the physiological mode of circulating progesterone in the rat. Further, in male rabbits, pulses of progesterone did not stimulate LHRH release. Last, probing the anterior pituitary with the PPC revealed that a series of push-pull perfusions could be performed in the same animal under different experimental conditions for nearly 60 days of experimentation. It also resolved the apparent paradox that after castration, decreased instead of increased activity of the neural LHRH apparatus was noticed when the PPC was positioned in the hypothalamus. Moving the PPC to the anterior pituitary revealed that castration was accompanied by an increase in the amplitude and frequency of the LHRH signals arriving in the anterior pituitary of castrated male rats. This mode of operation of the LHRH pulse generator is clearly compatible with the mode of luteinizing hormone (LH) release in gonadectomized animals. Finally, based on these results, a hypothetical model of the operation of the LHRH pulse generator has been proposed.

Animals↗

Involvement of olfactory bulb catecholamines and luteinizing hormone-releasing hormone in response to social stimuli mediating reproductive functions.

In this paper we summarize our findings related to the involvement of olfactory bulb (OB) catecholamines and LHRH in response to social stimuli. Previous work from our laboratory had indicated the presence of LHRH within the OB, with localization of this neuropeptide to the posterior dorsal area of this structure. Subsequent work has demonstrated that the presence and localization of LHRH within the OB is an ubiquitous phenomenon characteristic of several rodent species and appears specific for the neuropeptide LHRH, since TRH failed to demonstrate any comparable localization. Analysis of catecholamine concentrations by HPLC-EC revealed that norepinephrine was present in greatest concentrations. Changes in the concentration of LHRH within the OB were obtained following social or chemical cue stimulation. These changes were also localized to the posterior OB, appeared to be specific for LHRH (versus TRH) and were associated with changes in catecholamine concentrations. Recently, we have implanted a push-pull cannula in the OB of male rats and measured the in vivo release of these neuroactive substances in the awake freely moving rat. Release of LHRH from the OB was extremely low with most samples below the detectability of the assay. When detectable, the output of LHRH did not appear to be associated with the introduction of a receptive female. In contrast, norepinephrine output was obtained from all males and demonstrated marked increases in response to the introduction of a receptive female, suggesting that this neurotransmitter may be an important component for processing chemical cue information within the OB.

Animals↗

In vivo activity of the LHRH pulse generator as determined with push-pull perfusion of the anterior pituitary gland of unrestrained intact and castrate male rats.

In the present article we report that in vivo LHRH output as measured at the anterior pituitary following castration significantly increased, due to larger and more frequent LHRH signals arriving to this gland. This contrasts with the decreased amplitude and overall mean LHRH release of castrate males bearing a push-pull cannula within the hypothalamus. These divergent results have generated a new thesis regarding the role of gonadal steroids upon the LHRH pulse generator. This thesis submits that following castration there is an increased frequency and decreased amplitude of the LHRH signal from discrete loci within the medial basal hypothalamus, but an increased synchrony of LHRH release throughout the entire hypothalamus, resulting in an increased frequency and amplitude of LHRH arriving at the anterior pituitary.

Animals↗

Membrane mechanism mediates progesterone stimulatory effect on LHRH release from superfused rat hypothalami in vitro.

To determine whether the plasma membrane is a primary site for progesterone (P4) action on the neural LHRH apparatus of hypothalamic tissues derived from ovariectomized, estradiol-primed (OVX + E2) immature rats, immobilized P4 was infused directly to these tissues using a superfusion technique. Two kinds of immobilized P4 with bovine serum albumin (BSA) conjugated at positions 3 or 11, or 11-deoxycorticosterone (DOC) immobilized at position 21 of the steroid molecule, respectively, were tested for structural specificity. Among the three immobilized steroids, only P4 with BSA conjugated at position 3 (P4-3-BSA) was effective in stimulating LHRH release in vitro. P4-3-BSA at 0.5 micrograms/ml, approximately 1.7 X 10(-7) M of P4, increased LHRH levels in the superfusates to about 2.5-fold those of pretreatment levels. In addition, no conversion of P4-3-BSA to free progesterone was detected. This observation demonstrated that the plasma membrane is a primary site for the stimulating effect of P4 on LHRH release from hypothalamic tissue in vitro.

Animals↗

The nature and magnitude of in vivo 5-hydroxyindoleacetic acid output from 5-hydroxytryptamine terminals is related to specific regions of the suprachiasmatic nucleus.

Eight cycling female rats were implanted with push-pull cannulae over the region of the suprachiasmatic nuclei (SCN) and allowed 7-10 days for recovery. Perfusion of the SCN continued in these freely behaving rats for 5-6 h of the light period and the subjective scotophase. The release of 5-hydroxyindoleacetic acid (5-HIAA) ranged from 10 to 350 pg 5-HIAA/min. Significantly, the amplitude and characteristics of the output of 5-HIAA were highly location dependent in that rostral cannulae placements revealed high amplitude changes with initial mean values of 40 pg 5-HIAA/min, which increased toward the dark phase to mean peak values of 195 pg 5-HIAA/min. Caudal cannulae placements revealed a low amplitude, high frequency, basal type of 5-HIAA release which did not increase toward the dark period (approximately 5 pg/min). 5-Hydroxytryptophan infusion resulted in a significant marked increase in the basal release of 5-HIAA confirming the biochemical viability of the area undergoing perfusion. These results suggest that the in vivo measurement of 5-HIAA from 5-hydroxytryptamine (5-HT) terminals in the region of the SCN could reflect discrete functional activity of serotonergic terminals within specific regions of the SCN in a freely behaving rat. Furthermore, the biochemical viability of these 5-HT terminals and the ability of the rat's SCN to exhibit marked differential changes in 5-HT activity emphasizes the physiological relevance of this model system to study neuroendocrine events in freely behaving animals.

Animals↗

Circulating blood progesterone is pulsatile throughout the rat oestrous cycle.

In the present experiment, we determined circulating progesterone (P4) levels of intact cycling female rats. A cannula constructed from polyethylene 50 tubing containing heparinized saline was inserted into the jugular vein of the rat under light ether anaesthesia and after a 3-6 h recovery period sequential blood samples were withdrawn from unanaesthetized, freely-moving rats. Blood samples (80-100 microliter) were collected at 10-min intervals for 6 h and the volume was replaced with saline. Plasma P4 was determined using a specific P4 radioimmunoassay. Four rats in each of three phases of the rat oestrous cycle (E, D1, D2) were examined. In addition, rats in proestrus were divided into an early (EP, N = 4) and a late (LP, N = 4) proestrous conditions. Individual data were analyzed by PULSAR as adapted for an IBM-PC. P4 was found to fluctuate in a pulsatile mode throughout the rat oestrous cycle. Mean levels of circulating P4 were lowest (38.8 +/- 1.7 nmol/l plasma) in EP and highest (122.5 +/- 1.3) in D1. The frequency of P4 pulses was dramatically decreased in D1 (2.50 +/- 0.86 pulses/6 h), whereas no difference was found among the other days of the cycle (7.25 +/- 0.47 in E, 7.25 +/- 0.85 in D2, 5.75 +/- 1.31 in EP, and 6.50 +/- 1.04 in LP). Interestingly, the amplitude of P4 pulses was significantly lower in EP (14.0 +/- 2.91 pmol), whereas no difference was found among other groups. Another group of experimental animals were ovariectomized (N = 4; two with and two without an implant of a silastic capsule of P4) and similarly bled.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Daily changes in in vitro spontaneous dopamine efflux from the corpus striatum of male rats.

In the present experiment we examined the spontaneous in vitro dopamine (DA) efflux from superfused corpus striatum (CS) of male rats at 3-hr intervals throughout a 24-hr photoperiod (lights on 0500-1900 hr). Maximal mean efflux, and post-superfusion DA concentrations were obtained at 0600 hr. With the exception of 0600 hr, mean efflux was lower during the light compared to the dark phase. Interestingly, the direction of the efflux profiles also varied as a function of time demonstrating increasing, decreasing and relatively stable profiles over the superfusion period. These changes in overall mean efflux, post-superfusion tissue concentration and efflux rate profile direction indicate that circadian processes play a complex role upon the synthesis/release process of DA from the nigrostriatal dopaminergic system that is revealed under the dynamic conditions of in vitro superfusion of isolated CS fragments.

Animals↗

Effects of prostaglandin E2, forskolin and cholera toxin on cAMP production and in vitro LH-RH release from the rat hypothalamus.

The present study attempts to elucidate the possible role of adenosine 3',5'-monophosphate (cAMP) and prostaglandin E2 (PGE2) in the function of the neural luteinizing hormone-releasing hormone (LH-RH) apparatus. To this end, in vitro LH-RH release from superfused hypothalamic fragments and cAMP production by hypothalamic P2 membrane fractions were measured. Immature female rats (day 28) were ovariectomized and implanted with Silastic capsules containing estradiol (235 micrograms/ml). Two days later, animals were sacrificed and the mediobasal hypothalamic preoptic area (hypothalamic units or fragments) were removed. To examine in vitro LH-RH release from superfused hypothalamic fragments, effluents were collected into tubes on ice at 10-min intervals and LH-RH concentration was determined by radioimmunoassay (RIA). Following a 50-min control period, a step-wise increment in several doses of PGE2 (each dose for a 50-min interval) evoked a dose-related increase in LH-RH release. PGE2 induced significant (P less than 0.01) increments in LH-RH release at doses of 5.68 X 10(-7), 5.68 X 10(-6), and 5.68 X 10(-5) M, respectively. When adenylate cyclase activators, such as forskolin and cholera toxin were infused in a step-wise manner (each dose for a 50-min interval) following a 50-min control period, a dose-related increase in LH-RH release was also obtained; forskolin and cholera toxin significantly (P less than 0.01) stimulated LH-RH release at doses of 1 X 10(-4) and 5.4 X 10(-10) M, respectively. These two substances were ineffective in stimulating LH-RH release when hypothalamic fragments were superfused in calcium-free plus EGTA (10 mM) containing medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

The mechanism of action of MPTP and MPP+ on endogenous dopamine release from the rat corpus striatum superfused in vitro.

In this paper, using an in vitro superfusion system, we examined in the rat corpus striatum (CS) the action of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and N-methylphenylpyridine (MPP+) on dopamine (DA) metabolism. MPTP, at at 10(-5) M and 10(-4) M, caused decreases in 3,4-dihydroxyphenylacetic acid (DOPAC) output in a dose-dependent manner. In addition, at 10(-4) M, MPTP caused an increase in DA release from CS. On the other hand, at 10(-6) M and 10(-5) M, MPP+ exerted very potent and rapid inhibition on DOPAC output and stimulated DA release in a dose-dependent manner. Furthermore, pretreatment of MPP+ markedly potentiated K+-stimulated DA release from CS. From the present data, we propose that MPP+ (the active metabolite of MPTP) inhibits DA reuptake system and/or monoamine oxidase (MAO) activity, increases readily releasable pool of DA and stimulates DA release from dopaminergic terminals.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

The effect of hormonal condition on dose-dependent amphetamine-stimulated behaviors in the male rat.

The effects of varying doses (1.25, 2.5, and 5.0 mg/kg, ip) of D-amphetamine sulfate (AMPH) on eight individual behaviors (Rearing, Grooming, Sniffing, Stationary, Gnawing, Head Bobbing, "Sleeping," and Licking) of Castrate + Oil-treated, Castrate + Testosterone Propionate (TP)-treated, and Intact male rats were examined. For Stationary, Sniffing, and "Sleeping" at 1.25 mg/kg AMPH and Rearing and Sniffing at the 2.5 mg/kg dose a significantly greater duration in the behavioral score was obtained for Castrate + Oil versus Castrate + TP and Intact males. These results indicate the complexity of the AMPH dose-response effects upon measurable behaviors, the alteration in the duration of these effects as a function of the hormonal condition of the male rat, and the importance of examining discrete components of behavior when hormone-amphetamine interactions are examined.

Animals↗