A functional dimorphism in the response of the hypothalamic-pituitary axis of prepubertal rats to steroid treatment

In the present experiment we examined the circadian neural luteinizing hormone releasing hormone (LHRH) and serum luteinizing hormone (LH) response of prepubertal male and female rats under varying steroidal manipulations (Intact, Castrate, Castrate + estradiol 17 beta [E2] + oil and Castrate + E2 + progesterone[P]). Prepubertal males demonstrated greater and acyclic LHRH concentrations in both the medial basal hypothalamus (MBH) and preoptic-suprachiasmatic regions (POA-Sch) irrespective of steroid treatment. In steroid-treatment castrated male rats only the negative feedback action on serum LH levels were observed with maximal effect in animals injected with the combination E2 + P. In contrasts, prepuberal castrated females exhibited both inhibitory and stimulatory feedback actions on LH release following steroid treatment. Moreover, a distinctive, significant, progesterone-dependent increase in AM POA-Sch, but not MBH-LHRH concentrations was detected. These results demonstrate the existence of a functional sexual dimorphism in the positive feedback response of the POA-Sch-pituitary axis of prepubertal rats to progesterone treatment.     

Activation of serotonin (5-HT)1A receptors inhibits amphetamine sensitization in mice

The effects of serotonin (5-HT)1A drugs on the development and expression of sensitization to the locomotor effect of amphetamine (AMPH) were studied in mice. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A agonist, dose-dependently reduced the expression of AMPH (2.5 mg/kg)-induced sensitization. The latter inhibitory effect of 8-OH-DPAT was reversed by (S)-N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenyl propamine (WAY 100135), a 5-HT1A antagonist. WAY 100135 given alone did not affect expression of AMPH sensitization. Combined injections of 8-OH-DPAT, but not WAY 100135, with AMPH (2.5 mg/kg) during the development of sensitization, protected against the expression of sensitization to a challenge dose of AMPH (2.5 mg/kg) 3 days after withdrawal. The above inhibitory effect of 8-OH-DPAT on the development of AMPH sensitization was blocked by pretreatment with WAY 100135. The AMPH-induced conditioned locomotion was unaffected by pretreatment with 8-OH-DPAT. These results indicate that 5-HT1A receptors are not involved in AMPH-induced sensitization per-se, whereas their pharmacological activation leads to the inhibition of both the development and the expression of AMPH-induced sensitization.     

Toxicity of pure alkaloid of Tylophora asthamatica in male rat

Administration of pure alkaloid of T. asthamatica, suspended in peanut oil and given in single doses (12-100 mg/kg) by gavage, to male rats caused inactivity, respiratory distress, salivation, nasal discharge and diarrhoea. The oral LD50 value of the alkaloid was 35.32 mg/kg. In short term toxicity study daily doses of the alkaloid (1.25, 2.5, 5 and 10 mg/kg) were given to male rats for 15 days. Smaller doses of the alkaloid (1.25 and 2.5 mg/kg/day) produced no signs of poisoning or death in animals; while 5 mg/kg/day produced signs of poisoning and death of two animals, 10 mg/kg/day caused death of all the animals within 7 days. Activities of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline phosphatase were significant and associated with morphological changes in liver. The alkaloid also caused marked changes in the morphology of seminiferous tubules and spermatogenic activity of experimental animals. Since the alkaloid is effective in microgram quantities, the non toxic effects observed after daily doses of 1.25 mg/kg in male rats assume great therapeutic significance.     

Effect of propiomazine on plasma prolactin in the rat: counteraction by L-dopa

A single iv injection of 0.31, 0.62, 1.25, 2.5, 5, 10, or 20 mg/kg body wt of a phenothiazine derivative, propiomazine (PP), into male rats significantly (P less than 0.05) increased plasma prolactin concentrations. The higher doses (5, 10, and 20 mg/kg body wt) produced increases that were greater in both magnitude and duration than those produced by the lower doses. The higher doses of PP, along with the elevations in plasma prolactin, also produced concomitant decreases in plasma luteinizing hormone (LH) levels. Pretreatment with L-dopa (100 mg/kg body wt) completely blocked the PP-induced stimulation of prolactin release, indicating that antidopaminergic action of PP either at the hypothalamic or anterior pituitary level was responsible for its effects on the release of prolactin.     

重金属 Ni2+ 对亚洲玉米螟生长发育和生殖行为的影响

【目的】探索农田重金属Ni²⁺污染对植食性昆虫潜在的影响。【方法】在人工饲料中添加不同浓度（1, 5, 10, 15和20 mg/kg）的重金属Ni²⁺,以不添加重金属的人工饲料为对照,实验室条件下饲养亚洲玉米螟 Ostrinia furnacalis (Guenée)初孵幼虫,系统观察其各项生长发育和生殖行为指标参数。【结果】Ni ²⁺对亚洲玉米螟幼虫期、蛹期、化蛹率和羽化率有抑制作用;对亚洲玉米螟雌蛹重有促进作用,但随Ni²⁺浓度的升高而逐渐减弱;低浓度Ni²⁺（1~10 mg/kg）对雄蛹重有促进作用,高浓度Ni²⁺（15~20 mg/kg）对雄蛹重有抑制作用。随着Ni²⁺浓度的增加,亚洲玉米螟雌蛾平均求偶持续时间逐渐减小;1 mg/kg Ni²⁺浓度下雌蛾求偶率及求偶高峰期出现的时间与对照组基本一致,其余4个Ni²⁺浓度都对雌蛾求偶行为产生影响且表现为求偶高峰期出现的时间提前,最高求偶率均小于100%。5 mg/kg Ni²⁺对亚洲玉米螟雄蛾定向行为有促进作用,其余浓度则表现为抑制作用。Ni²⁺对亚洲玉米螟雌蛾的产卵量和卵孵化率均产生了显著的抑制作用。【结论】重金属Ni²⁺对亚洲玉米螟的生长发育和生殖行为产生了影响。     

p-Chloroamphetamine (PCA) suppresses ingestive behavior in male rats.

Ingestive behavior was activated in male rats by intraoral intake and intake from a bottle of 1-M solution of sucrose. Intraperitoneal injection of p-chloroamphetamine (PCA), releasing central 5-hydroxytryptamine (5-HT) from serotonergic nerve terminals, inhibited ingestion of the sucrose solution. Significant inhibition of sucrose intake by PCA was observed at 1.25 and 2.5 mg/kg dose in a bottle intake test, and at 5.0 mg/kg dose in an intraoral intake test. These findings suggested that 1.25 and 5.0 mg/kg of PCA suppressed appetitive ingestive behavior and consummatory ingestive behavior in male rats, respectively.     

Effects of chronic administration of phencyclidine on stereotyped and ataxic behaviors in the rat

After chronic administration of Phencyclidine (PCP) to rats, a high test dose (15 mg/kg) of PCP produced increases in stereotypic and ataxic behaviors, and a lower test dose of PCP (5 mg/kg) produced decreases in these behaviors, compared to behavioral responses of control rats. Rearing behavior in rats chronically administered PCP was increased at all test doses of the drug. Rats treated chronically with 15 mg/kg PCP for 9 days showed marked increases in most of these behaviors, whereas, rats receiving 5 mg/kg PCP for 9 days showed less change in several stereotypic and ataxic behaviors. Rats receiving 10 mg/kg PCP on a once-weekly schedule also exhibited more rearing and ataxic behavioral responses after the 3rd or 4th weekly PCP injection. Chronic PCP rats did not show more stereotypic or ataxic behavior after administration of apomorphine or amphetamine than control rats. These results suggest that chronic administration of PCP augments sensitivity to the stereotypic inducing effects of high doses, and decreases sensitivity to low doses of PCP.     

Lack of effects of glycineB receptor ligands on the psychostimulant-induced discriminative stimuli in rats

To examine the role of glycineB receptors in the stimulus effects induced by psychostimulants, separate groups of rats were trained to discriminate amphetamine (AMPH; 1 mg/kg) from saline (SAL), or cocaine (COC; 10 mg/kg) from SAL, using a two-lever operant procedure. Substitution studies showed that neither 1-aminocyclopropanecarboxylic acid (ACPC; 200 mg/kg) nor 7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-(H)quinolone (L-701,324; 3 mg/kg), being a partial agonist or an antagonist at glycineB receptors, respectively, generalized for the training drugs. Combination tests of glycineB ligands demonstrated that injection of a fixed dose of ACPC (200 mg/kg) or L-701,324 (3 mg/kg) together with different doses of AMPH or COC practically did not modify dose-response curves of the psychostimulants, nor did it affect their ED50 values. Our results indicate that glycineB receptors do not play a role in the discriminative effects of AMPH and COC.     

Photoperiod modulates pubertal shifts in behavioral responsiveness to testosterone.

This study examined the effect of photoperiod on pubertal maturation of steroid-dependent reproductive behaviors in male European ferrets (Mustela putorius furo). In the first experiment, levels of neck gripping, mounting, and pelvic thrusting in gonadally intact prepubertal (PRE) ferrets were compared with those of adults that had undergone puberty either while housed in short days (8 hr light/16 hr darkness per day; SD), or after transfer from SD to long days (18 hr light/6 hr darkness per day; LD) at 12 weeks of age. Both LD and SD adults demonstrated significantly greater amounts of neck gripping and mounting than PRE males. In addition, a significantly greater proportion of adults in both SD and LD displayed at least one incidence of the three behaviors compared to PRE ferrets. There were no statistically significant differences in behavior of the gonadally intact LD and SD adults. In the second experiment, dose-response curves for behavioral responses to subcutaneous injections of 0, 0.5, 1.25, 2.5, 5, and 10 mg/kg testosterone propionate (TP) in oil were generated in castrated PRE, SD, and LD males. The lowest dose of TP elicited significantly greater amounts of all three behaviors in LD adults than in PRE ferrets. In addition, levels of mounting and thrusting elicited by the lowest dose of TP were significantly greater in LD adults than in SD adults. These data indicate that pubertal activation of male sexual behavior in male ferrets is accompanied by a pubertal increase in responsiveness to the behavioral effects of testosterone. Furthermore, the degree of behavioral responsiveness of adult ferrets to testosterone is modulated by environmental photoperiod experienced during reproductive maturation.     

CART peptide 55-102 microinjected into the nucleus accumbens inhibits the expression of behavioral sensitization by amphetamine

CART peptide has been shown to regulate the actions of psychomotor stimulants. Here we have further investigated the role of the biologically active CART 55-102 peptide in the nucleus accumbens (NAcc) in the expression of behavioral sensitization by amphetamine (AMPH). Rats were pre-exposed 5 times to either saline or AMPH (1 mg/kg, i.p.). After 2 weeks of withdrawal, rats were microinjected into the NAcc with saline or CART 55-102 (1.0, or 2.5 microg/0.5 microl/side) followed by AMPH challenge (1 mg/kg, i.p.). The enhanced increase of locomotion and rearing produced by repeated AMPH pre-exposures was dose-dependently inhibited by microinjection into the NAcc of CART 55-102 peptide. These results indicate that CART 55-102 peptide in the NAcc can play a compensatory inhibitory role in the expression of behavioral sensitization by AMPH and further suggest that CART peptide may be a useful target to control the drug addiction by psychomotor stimulants.     

Threshold for behavioral response to testosterone in old castrated male rhesus macaques

The sexual behaviors of old, intact (N = 5) and old, castrated (N = 6) rhesus macaque males were compared in six series of pair tests with receptive females. The castrated monkeys were tested when untreated and when given five doses of testosterone propionate (TP; 0.004, 0.016, 0.064, 0.256, and 1.024 mg/kg of body weight) in consecutive months. The serum testosterone (T) level was determined for each male before and after each series of tests. When untreated, none of the castrated males ejaculated, and yawning was significantly less in these monkeys than in intact males-no other behavioral measures differed significantly. Within 2 weeks of daily injections of 0.004 mg of TP/kg, two males ejaculated, and all differences in measures of ejaculation were eliminated. A third male ejaculated after 1 week of treatment with 0.016 mg of TP/kg. Yawning values did not differ during and after treatment with 0.064 mg of TP/kg. Although final mean serum T levels were six times higher in castrated (24.3 ng/ml) than in intact males (4.2 ng/ml), sexual performance levels did not exceed those of intact males.     

High doses of amphetamine augment, rather than disrupt, exocytotic dopamine release in the dorsal and ventral striatum of the anesthetized rat

High doses of amphetamine (AMPH) are thought to disrupt normal patterns of action potential-dependent dopaminergic neurotransmission by depleting vesicular stores of dopamine (DA) and inducing robust non-exocytotic DA release or efflux via dopamine transporter (DAT) reversal. However, these cardinal AMPH actions have been difficult to establish definitively in vivo. Here, we use fast-scan cyclic voltammetry (FSCV) in the urethane-anesthetized rat to evaluate the effects of 10 and 20 mg/kg AMPH on vesicular DA release and DAT function in dorsal and ventral striata. An equivalent high dose of cocaine (40 mg/kg) was also examined for comparison to psychostimulants acting preferentially by DAT inhibition. Parameters describing exocytotic DA release and neuronal DA uptake were determined from dynamic DA signals evoked by mild electrical stimulation previously established to be reinforcing. High-sensitivity FSCV with nanomolar detection was used to monitor changes in the background voltammetric signal as an index of DA efflux. Both doses of AMPH and cocaine markedly elevated evoked DA levels over the entire 2-h time course in the dorsal and ventral striatum. These increases were mediated by augmented vesicular DA release and diminished DA uptake typically acting concurrently. AMPH, but not cocaine, induced a slow, DA-like rise in some baseline recordings. However, this effect was highly variable in amplitude and duration, modest, and generally not present at all. These data thus describe a mechanistically similar activation of action potential-dependent dopaminergic neurotransmission by AMPH and cocaine in vivo. Moreover, DA efflux appears to be a unique, but secondary, AMPH action.     

Ultrasonic vocalization in response to unavoidable aversive stimuli in rats: effects of benzodiazepines

The effects of two benzodiazepine derivatives (diazepam, 0.5-1 mg/kg; alprazolam, 1.25-2.5 mg/kg) on ultrasonic calling elicited in adult rats by unavoidable aversive stimuli (footshocks) were investigated. The results show that either diazepam or alprazolam affected the duration of ultrasonic calls. In particular, a significant decrease in the length of ultrasounds was found in the group of animals treated with these benzodiazepines. The effects of diazepam were counteracted by the benzodiazepine-antagonist Ro 15-1788. On the other hand, neither a neuroleptic agent, such as haloperidol (0.5-1 mg/kg), nor an antidepressant, such as desipramine (5-10 mg/kg) influenced the parameters of ultrasonic emission in this experimental situation. The present results suggest that ultrasonic vocalization in response to unavoidable aversive stimuli could be considered as a potential new tool for studying drugs with antianxiety properties.     

7-Nitroindazole enhances amphetamine-evoked dopamine release in rat striatum. an in vivo microdialysis and voltammetric study.

The intracellular second messenger nitric oxide (NO) is implicated in a variety of physiological functions, including release and uptake of dopamine (DA). In the described study, in vivo microdialysis and differential pulse voltammetric techniques were used to determine the involvement of NO in release of DA and its metabolites (dihydroxyphenylalanine, DOPAC; homovanillic acid, HVA) in neostriatum of freely moving rats. While the NO donor molsidomine (30.0 mg/kg; MOLS) and neuronal NO synthase- (nNOS-) inhbitor 7-nitroindazole (10.0 mg/kg; 7-NI) had no effect on the basal in vivo microdialysate level of DA, 7-NI specifically enhanced D,L-amphetamine-(1.0 mg/kg i.p.; AMPH) evoked release of DA. Basal or AMPH effects on DOPAC and HVA levels were not influenced by MOLS or 7-NI. Findings indicate that nitrergic systems have an important role in mediating effects of AMPH on dopaminergic systems.     

Amphetamine and chlorpromazine modify cerebral insulin levels in rats

Rats treated with chlorpromazine (CPZ) (1 mg/kg/day i.p.) experienced a marked decline in cerebral insulin levels (0.057 +/- 0.01 ng/g wet weight) with respect to a control group (0.38 +/- 0.05 ng/g wet weight), while rats given D-amphetamine bitartrate (AMPH) chronically (20 mg/kg/day p.o.) showed a rise in cerebral insulin (0.55 +/- 0.04 ng/g wet weight). Combined treatment with both drugs at the same dosages produced lower cerebral insulin levels (0.46 +/- 0.10 ng/g wet weight) than in the AMPH animals. In the groups of rats treated with CPZ and with AMPH + CPZ, there was a slight elevation in serum insulin levels. Serum glucose values did not vary.     

Amphetamine and Methamphetamine Differentially Affect Dopamine Transporters in Vitro and in Vivo

The psychostimulants d-amphetamine (AMPH) and methamphetamine (METH) release excess dopamine (DA) into the synaptic clefts of dopaminergic neurons. Abnormal DA release is thought to occur by reverse transport through the DA transporter (DAT), and it is believed to underlie the severe behavioral effects of these drugs. Here we compare structurally similar AMPH and METH on DAT function in a heterologous expression system and in an animal model. In the in vitro expression system, DAT-mediated whole-cell currents were greater for METH stimulation than for AMPH. At the same voltage and concentration, METH released five times more DA than AMPH and did so at physiological membrane potentials. At maximally effective concentrations, METH released twice as much [Ca²⁺]_i from internal stores compared with AMPH. [Ca²⁺]_i responses to both drugs were independent of membrane voltage but inhibited by DAT antagonists. Intact phosphorylation sites in the N-terminal domain of DAT were required for the AMPH- and METH-induced increase in [Ca²⁺]_i and for the enhanced effects of METH on [Ca²⁺]_i elevation. Calmodulin-dependent protein kinase II and protein kinase C inhibitors alone or in combination also blocked AMPH- or METH-induced Ca²⁺ responses. Finally, in the rat nucleus accumbens, in vivo voltammetry showed that systemic application of METH inhibited DAT-mediated DA clearance more efficiently than AMPH, resulting in excess external DA. Together these data demonstrate that METH has a stronger effect on DAT-mediated cell physiology than AMPH, which may contribute to the euphoric and addictive properties of METH compared with AMPH.The dopamine transporter (DAT)³ is a main target for psychostimulants, such as d-amphetamine (AMPH), methamphetamine (METH), cocaine (COC), and methylphenidate (Ritalin®). DAT is the major clearance mechanism for synaptic dopamine (DA) (1) and thereby regulates the strength and duration of dopaminergic signaling. AMPH and METH are substrates for DAT and competitively inhibit DA uptake (2, 3) and release DA through reverse transport (4–9). AMPH- and METH-induced elevations in extracellular DA result in complex neurochemical changes and profound psychiatric effects (2, 10–16). Despite their structural and pharmacokinetic similarities, a recent National Institute on Drug Abuse report describes METH as a more potent stimulant than AMPH with longer lasting effects at comparable doses (17). Although the route of METH administration and its availability must contribute to the almost four times higher lifetime nonmedical use of METH compared with AMPH (18), there may also be differences in the mechanisms that underlie the actions of these two drugs on the dopamine transporter.Recent studies by Joyce et al. (19) have shown that compared with d-AMPH alone, the combination of d- and l-AMPH in Adderall® significantly prolonged the time course of extracellular DA in vivo. These experiments demonstrate that subtle structural features of AMPH, such as chirality, can affect its action on dopamine transporters. Here we investigate whether METH, a more lipophilic analog of AMPH, affects DAT differently than AMPH, particularly in regard to stimulated DA efflux.METH and AMPH have been reported as equally effective in increasing extracellular DA levels in rodent dorsal striatum (dSTR), nucleus accumbens (NAc) (10, 14, 20), striatal synaptosomes, and DAT-expressing cells in vitro (3, 6). John and Jones (21), however, have recently shown in mouse striatal and substantia nigra slices, that AMPH is a more potent inhibitor of DA uptake than METH. On the other hand, in synaptosomes METH inhibits DA uptake three times more effectively than AMPH (14), and in DAT-expressing COS-7 cells, METH releases DA more potently than AMPH (EC₅₀ = 0.2 μm for METH versus EC₅₀ = 1.7 μm for AMPH) (5). However, these differences do not hold up under all conditions. For example, in a study utilizing C6 cells, the disparity between AMPH and METH was not found (12).The variations in AMPH and METH data extend to animal models. AMPH- and METH-mediated behavior has been reported as similar (22), lower (20), or higher (23) for AMPH compared with METH. Furthermore, although the maximal locomotor activation response was less for METH than for AMPH at a lower dose (2 mg/kg, intraperitoneal), both drugs decreased locomotor activity at a higher dose (4 mg/kg) (20). In contrast, in the presence of a salient stimuli, METH is more potent in increasing the overall magnitude of locomotor activity in rats yet is equipotent with AMPH in the absence of these stimuli (23).The simultaneous regulation of DA uptake and efflux by DAT substrates such as AMPH and METH, as well as the voltage dependence of DAT (24), may confound the interpretation of existing data describing the action of these drugs. Our biophysical approaches allowed us to significantly decrease the contribution of DA uptake and more accurately determine DAT-mediated DA efflux with millisecond time resolution. We have thus exploited time-resolved, whole-cell voltage clamp in combination with in vitro and in vivo microamperometry and Ca²⁺ imaging to compare the impact of METH and AMPH on DAT function and determine the consequence of these interactions on cell physiology.We find that near the resting potential, METH is more effective than AMPH in stimulating DAT to release DA. In addition, at efficacious concentrations METH generates more current, greater DA efflux, and higher Ca²⁺ release from internal stores than AMPH. Both METH-induced or the lesser AMPH-induced increase in intracellular Ca²⁺ are independent of membrane potential. The additional Ca²⁺ response induced by METH requires intact phosphorylation sites in the N-terminal domain of DAT. Finally, our in vivo voltammetry data indicate that METH inhibits clearance of locally applied DA more effectively than AMPH in the rat nucleus accumbens, which plays an important role in reward and addiction, but not in the dorsal striatum, which is involved in a variety of cognitive functions. Taken together these data imply that AMPH and METH have distinguishable effects on DAT that can be shown both at the molecular level and in vivo, and are likely to be implicated in the relative euphoric and addictive properties of these two psychostimulants.     

Amphetamine modulates human incentive processing

Research suggests that psychostimulants can physiologically alter dopamine kinetics in the ventral striatum (VS) and psychologically enhance mood and attention. Using event-related functional magnetic resonance imaging (fMRI), we conducted a within-subject, double-blind, placebo (PLAC)-controlled study of the effects of oral dextroamphetamine (AMPH, 0.25 mg/kg) treatment on brain activity and affect during incentive processing. In two counterbalanced scanning sessions 60-180 min after ingesting AMPH or PLAC, 8 healthy volunteers played a game involving anticipation and receipt of monetary gains and losses. Group and volume of interest analyses suggested that by enhancing tonic over phasic activation, AMPH treatment "equalized" levels of VS activity and positive arousal during anticipation of both gain and loss. These findings suggest that therapeutic effects of amphetamine on incentive processing may involve reducing the difference between anticipation of gains and losses.     

Amphetamine induced sensitization in acoustic startle: lack of blockade by adrenalectomy and alpha-helical CRF9-41

The present study utilized the acoustic startle response to evaluate the sensitization effect of repeated administration of amphetamine (AMPH). Intraperitoneal injections of AMPH induced a dose-dependent enhancement of startle: 5.0 mg/kg caused a robust effect, 1.0 or 3.0 mg/kg caused a negligible effect. Sensitization was generated by repeated administration of 5.0 mg/kg AMPH for 7 consecutive days and tested on the 8th and 9th days with challenge of saline and 3 mg/kg AMPH. The results showed that rats receiving chronic injections of AMPH, but not saline, showed significant enhancement of startle to 3.0 mg/kg AMPH, and this effect lasted at least for a month. To explore the role of the hypothalamo-pituitary-adrenal axis in this sensitization effect, rats received adrenalectomy, adrenal demedullation, or sham adrenal operation, and then were subjected to acute or chronic injections of 5.0 mg/kg AMPH. Removal of the whole adrenal gland or only the medulla abolished neither the startle enhancing effect of AMPH injected acutely nor the sensitization effect of AMPH injected chronically. In addition, intracerebroventricular infusion of a CRF antagonist, alpha-helical CRF9-41, prior to the challenge test failed to alter the sensitization effect of AMPH. These findings suggest that neither adrenal hormones nor CRF was indispensable for induction/expression of AMPH-induced sensitization in acoustic startle.     

Amphetamine-Induced Dopamine Release in the Rat Striatum: An In Vivo Microdialysis Study

The effects of a number of biochemical and pharmacological manipulations on amphetamine (AMPH)-induced alterations in dopamine (DA) release and metabolism were examined in the rat striatum using the in vivo brain microdialysis method. Basal striatal dialysate concentrations were: DA, 7 nM; dihydroxyphenylacetic acid (DOPAC), 850 nM; homovanillic acid (HVA), 500 nM; 5-hydroxyindoleacetic acid (5-HIAA), 300 nM; and 3-methoxytyramine (3-MT), 3 nM. Intraperitoneal injection of AMPH (4 mg/kg) induced a substantial increase in DA efflux, which attained its maximum response 20-40 min after drug injection. On the other hand, DOPAC and HVA efflux declined following AMPH. The DA response, but not those of DOPAC and HVA, was dose dependent within the range of AMPH tested (2-16 mg/kg). High doses of AMPH (greater than 8 mg/kg) also decreased 5-HIAA and increased 3-MT efflux. Depletion of vesicular stores of DA using reserpine did not affect significantly AMPH-induced dopamine efflux. In contrast, prior inhibition of catecholamine synthesis, using alpha-methyl-p-tyrosine, proved to be an effective inhibitor of AMPH-evoked DA release (less than 35% of control). Moreover, the DA releasing action of AMPH was facilitated in pargyline-pretreated animals (220% of control). These data suggest that AMPH releases preferentially a newly synthesised pool of DA. Nomifensine, a DA uptake inhibitor, was an effective inhibitor of AMPH-induced DA efflux (18% of control). On the other hand, this action of AMPH was facilitated by veratrine and ouabain (200-210% of control). These results suggest that the membrane DA carrier may be involved in the actions of AMPH on DA efflux.     

Dopaminergic mediation of the diuretic and natriuretic action of centrally administered rat atrial natriuretic factor (99-126)

Intracerebroventricular administration of either rat atrial natriuretic factor (99-126) or dopamine to conscious male hydrated rats resulted in an increase in urinaryvolume and sodium excretion. This activity was prevented, in both cases, by nonselective dopamine antagonist haloperidol (2.5 or 1.25 mg/kg sc, 18 and 2 hr before intracerebroventricular administration of atrial natriuretic factor). Our findings suggest that atrial natriuretic factor exerts its centrally mediated effects on sodium and water metabolism, at least in part, via a dopaminergic mechanism.