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At least 307 records · Page 17Linked to original sources
PubMed1998

Injection of the protein kinase C inhibitor Ro31-8220 into the nucleus accumbens attenuates the acute response to amphetamine: tissue and behavioral studies.

The ability of amphetamine to produce heightened locomotor activity is thought to be due to its ability to enhance dopamine release from mesolimbic dopamine neurons. The mechanism by which amphetamine increases dopamine release is not well understood, but is thought to involve exchange diffusion with synaptosomal dopamine through the dopamine transporter. We recently reported that amphetamine-mediated dopamine release in the striatum is also dependent on protein kinase C activity. In the current study, we investigated the role of protein kinase C activity in the acute neurochemical and behavioral response to amphetamine in the nucleus accumbens. Consistent with previous results in the striatum, amphetamine-stimulated dopamine release from nucleus accumbens tissue was inhibited by the specific protein kinase C inhibitor Ro31-8220, but not by the relatively inactive analog bisindoylmaleimide V. In addition, the effects of protein kinase C activity on the acute behavioral response to amphetamine was examined by injecting Ro31-8220 into the nucleus accumbens 15 min prior to intra-accumbens amphetamine. Pretreatment with Ro31-8220 attenuated the motor-stimulant effects of intra-accumbens amphetamine relative to control subjects pretreated with vehicle. Bisindoylmaleimide V did not significantly inhibit the motor-stimulant effects of intra-accumbens amphetamine. These results suggest that the action of amphetamine in the nucleus accumbens in increasing dopamine release and locomotor activity is dependent on protein kinase C activity.

Amphetamine↗
PubMed2001

Significance of glutamate and dopamine neurons in the ventral pallidum in the expression of behavioral sensitization to amphetamine.

To explore the significance of ventral pallidum (VP) during the amphetamine sensitization, we first investigated if there are neurochemical alterations in the VP during amphetamine withdrawal period. Chronic amphetamine-treated (5 mg/kg x 14 days) rats displayed an apparent locomotion sensitization as compared with saline controls when challenged with 2 mg/kg amphetamine at withdrawal days 10-14. A microdialysis analysis revealed that output of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, in the VP of amphetamine-sensitized rats increased approximately two-fold as compared to controls at both pre- and post-amphetamine challenge period. On the other hand, the in vivo glutamate output in the VP increased upon amphetamine challenge in the behaviorally sensitized rats, but not in the controls. To evaluate if drug manipulation in the VP would affect the behavioral sensitization, we treated both groups of rats with NMDA receptor antagonist, MK-801 (5 microg/microl for 5 days; bilateral) in the VP during withdrawal days 6-10. Animals were challenged with 2 mg/kg amphetamine at withdrawal day 11. The behavioral profile exhibited that MK-801 pre-treatment significantly blocked the locomotion hyperactivity in amphetamine-sensitized rats. Taken together, the current results suggest that the excitatory amino acid in the VP plays a significant role during the expression of behavioral sensitization to amphetamine.

Amphetamine↗
PubMed2003

Effects of amphetamine on steroidogenesis in MA-10 mouse Leydig tumor cells.

Amphetamine influences plasma and testicular testosterone levels. However, there is no evidence that amphetamine can directly influence Leydig cell functions. In the present study, a MA-10 mouse Leydig tumor cell line was used to determine whether and how amphetamine affected Leydig cell steroidogenesis. MA-10 cells were treated with different concentrations of amphetamine without or with human chorionic gonadotropin (hCG) and/or enzyme precursors over different time durations. Steroid production, enzyme activities and StAR protein expression were determined. Amphetamine alone had no any effect on MA-10 cell steroidogenesis. However, amphetamine (10(-11)M and 10(-10)M) significantly enhanced hCG-treated progesterone production at 3 hr in MA-10 cells (p < 0.05). Furthermore, amphetamine significantly induced more progesterone production upon treatment with 22R-hydroxycholesterol (p < 0.05), a precursor of P450 side-chain cleavage enzyme (P450scc). However, amphetamine did not induce more progesterone production when treated with pregnenolone (p > 0.05), a precursor of 3beta-hydroxysteroid dehydrogenase. In addition, the expressions of StAR protein and P450scc enzyme were not significantly different between hCG alone and hCG plus amphetamine treatment in MA-10 cells (p > 0.05). These results suggested that amphetamine enhanced hCG-induced progesterone production in MA-10 cells by increasing P450scc activity without influencing StAR protein and P450scc enzyme expression or 3beta-HSD enzyme activity.

3-Hydroxysteroid Dehydrogenases↗
PubMed1997

5-HT2A/2C receptor agonists potentiate the discriminative cue of (+)-amphetamine in the rat.

The possible effect of 5-HT2A/2C receptor agonists on an amphetamine-induced behavioral response was examined using the two-lever drug discrimination paradigm. The experiments were designed to investigate an interaction of the hallucinogenic 5-HT2A/2C agonists lysergic acid diethylamide (LSD) and 2,5-dimethoxy-4-iodoamphetamine (DOI), with the discriminative stimulus elicited by a relatively low dose of (+)-amphetamine (1.35 micromol/kg, 0.25 mg/kg, which produced approximately 50% selection of the drug lever). DOI and LSD did not produce amphetamine-like responding at any dose tested or time of administration. However, LSD alone was able to induce a drug-appropriate response in two of nine amphetamine-trained rats. Simultaneous administration of DOI or LSD with amphetamine was not significantly different from the response produced by amphetamine alone. Pre-administration of DOI (3 hr) or of LSD (2 hr) before amphetamine, however, evoked significant enhancement of the amphetamine cue. The results suggest that the enhanced behavioral response to amphetamine may be due either to an increased sensitivity of dopaminergic neurons in the mesolimbic area, or to an enhanced release of dopamine by amphetamine.

Amphetamine↗
PubMed1999

Amphetamine reverses or blocks the operation of the human noradrenaline transporter depending on its concentration: superfusion studies on transfected cells.

Whether amphetamine enhances noradrenergic activity by uptake blockade or a releasing action is still a matter of debate. In order to gain insight into the interaction of amphetamine with the noradrenaline transporter its cDNA was transfected into COS-7 cells (NAT-cells) or cotransfected with the cDNA of the vesicular monoamine transporter (NAT/VMAT-cells); cells were loaded with [3H]noradrenaline, superfused and the efflux analysed for total tritium and [3H]noradrenaline. In NAT-cells amphetamine stimulated [3H]noradrenaline efflux concentration-dependently when added to the superfusion buffer at 0.01, 0.1 and 1 microM. By contrast, 10 or 100 microM amphetamine stimulated efflux to a smaller extent or not at all; however, on switching back to amphetamine-free buffer a prompt increase of efflux was observed. Cocaine did not increase efflux per se and blocked the amphetamine-induced efflux. In NAT/VMAT-cells amphetamine stimulated efflux in a concentration-dependent manner. The effect showed saturation at 1 microM and was not suppressed at higher concentrations. Cocaine also elicited efflux from NAT/VMAT-cells concentration-dependently; the maximum was reached at approximately 1 microM and amounted to only about half of the amphetamine-induced efflux. It is concluded that amphetamine can induce noradrenaline transporter mediated release only at high nanomolar to low micromolar concentrations. At higher concentrations it blocks the noradrenaline transporter; in this case, the releasing action of amphetamine, like that of cocaine, is dependent on a vesicular pool of noradrenaline.

Amphetamine↗
PubMed2000

Effects of serotonergic manipulations on the behavioral sensitization and disinhibition associated with repeated amphetamine treatment.

This study investigated the effects of repeated amphetamine treatment on locomotor activity and behavioral inhibition in the elevated plus-maze, and the influence of serotonin (5-HT) neurotransmission on these behaviors. Acute administration of amphetamine (1.0 mg/kg subcutaneously [SC]) stimulated locomotor activity, which was attenuated by acute citalopram (5.0 mg/kg SC) pretreatment. Repeated daily treatment with amphetamine (15 days) sensitized the rats to the amphetamine-induced locomotor stimulation. Acute pretreatment with the 5-HT precursor l-5-hydroxytryptophan (5-HTP; 25 mg/kg IP) or chronic treatment with the selective 5-HT reuptake inhibitor citalopram (5.0 mg/kg SC, twice daily), did not alter the expression of amphetamine-induced locomotor sensitization. In the elevated plus-maze, animals subjected to repeated amphetamine treatment expressed behavioral disinhibition after amphetamine exposure (1.0 mg/kg SC; -35 min), which was antagonized both by acute 5-HTP and chronic citalopram treatment. In summary, these findings suggest that behavioral sensitization to amphetamine is associated with amphetamine-induced behavioral disinhibition, and that acute 5-HTP as well as chronic citalopram treatment counteract the expression of amphetamine-induced behavioral disinhibition, but not locomotor sensitization. It appears likely that the antagonistic effects of 5-HTP and citalopram on behavioral disinhibition derive from a drug-induced facilitation of brain 5-HT neurotransmission.

5-Hydroxytryptophan↗
PubMed2001

Amphetamine administration does not alter protein levels of the GLT-1 and EAAC1 glutamate transporter subtypes in rat midbrain, nucleus accumbens, striatum, or prefrontal cortex.

Our laboratory and others have previously shown that glutamate transmission is required for chronic amphetamine-induced neuroadaptations, and that glutamate transmission itself is altered by chronic amphetamine administration. For example, N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor subunit expression are altered in a region- and withdrawal-specific manner. The goal of this study was to determine whether repeated amphetamine administration influences the expression of two glutamate transporter subtypes, GLT-1 and EAAC1. Rats were treated with saline or 5 mg/kg amphetamine for 5 days (chronic saline and amphetamine groups, respectively), or saline for 4 days and 5 mg/kg amphetamine on day 5 (acute amphetamine group), and decapitated 24 h after the last injection. Tissue was dissected from brain regions involved in the psychomotor effects of amphetamine (nucleus accumbens, striatum, prefrontal cortex, ventral tegmental area, and substantia nigra). Levels of GLT-1 and EAAC1 were quantified by Western blotting and normalized to actin levels. We found no significant change in levels of GLT-1 or EAAC1 in response to either acute or chronic amphetamine treatment. These findings suggest that the transporter component of the glutamate system might not play a significant role in the alterations in glutamate transmission observed following repeated amphetamine administration.

ATP-Binding Cassette Transporters↗
PubMed2002

Comparison of effects of khat extract and amphetamine on motor behaviors in mice.

The aim of this study was to determine if the psychostimulants, khat and amphetamine, exert similar effects in two tests of motor behaviors. Dose-response relationships were obtained for khat extract and D- and L-amphetamine given to mice by the intragastric route. Head twitch responses were significantly increased by khat and amphetamines. The latter were more potent than khat; dose-response curves for amphetamines had inverted U shapes. Khat extract decreased spontaneous motor activity, as measured by a photoactometer. Effects of amphetamines in this test were more variable and subject to dose dependent reversal. Other behaviors produced by higher doses of amphetamines interfered with specific motor responses under evaluation. Pretreatment with methysergide, a serotonin antagonist, significantly blocked head twitch responses but not spontaneous activity. Conversely, pretreatment with haloperidol decanoate, a dopamine receptor antagonist, prevented inhibition of spontaneous motor activity ordinarily evoked by khat and low dose D-amphetamine. We conclude that motor effects of khat and amphetamine resemble one another, but only at certain doses. Unlike khat, amphetamine causes additional behaviors that obscure motor responses of the types examined here. Results with transmitter receptor blockers suggest that motor effects of khat, like those of amphetamine, may be modulated by serotonin and dopamine.

Amphetamine↗
PubMed1998

Inhibition of gastric emptying and intestinal transit by amphetamine through a mechanism involving an increased secretion of CCK in male rats.

1. The effect of amphetamine on gastrointestinal (GI) transit and the plasma levels of cholecystokinin (CCK) were studied in male rats. 2. Gastric emptying was inhibited both acutely and chronically by the administration of amphetamine. GI transit was decreased by the acute administration of amphetamine but not affected by the chronic administration of amphetamine. 3. Plasma CCK levels were increased dose-dependently by amphetamine. 4. Proglumide, a CCK receptor antagonist, prevented amphetamine-induced inhibition of gastric emptying and the decrease in GI transit in male rats. 5. The selective CCK(A) receptor antagonist, lorglumide, dose-dependently attenuated the amphetamine-induced inhibition of gastric emptying in male rats. In contrast, the selective CCK(B) receptor antagonist, PD 135,158, did not reverse the effect of amphetamine on gastric emptying. 6. Both lorglumide and PD 135,158 reversed the inhibitory effect of amphetamine on GI transit in male rats. 7. These results suggest that amphetamine-induced inhibition of gastric emptying and intestinal transit is due in part to a mechanism associated with the hypersecretion of endogenous CCK.

Amphetamines↗
PubMed1999

Electrophysiological evidence for a reciprocal interaction between amphetamine and cocaine-related drugs on rat midbrain dopaminergic neurons.

To determine the functional interactions occurring between amphetamine and cocaine-like drugs on a single neuron, we used intracellular single-electrode voltage-clamp recordings from dopaminergic cells of the rat midbrain maintained in vitro. In the presence of cocaine (3-30 microM), the outward current caused by amphetamine (100 microM) on cells held at about -60 mV was attenuated. The degree of attenuation of the amphetamine-induced response was almost the same for 3 and 30 microM cocaine (44 and 51% of control, respectively). This effect of cocaine was reversible. We also tested other DA-uptake inhibitors (nomifensine and 4-phenyltetrahydroisoquinoline) against the amphetamine-induced outward current. Both drugs enhanced the effects of dopamine (DA) while reducing the outward response caused by amphetamine. Pretreatment of the animals with reserpine (12 mg/kg/i.p.), which irreversibly depletes the vesicular DA stores, neither affected the amplitude of the current caused by amphetamine nor changed the cocaine-induced attenuation of the membrane responses to amphetamine. Interestingly, when amphetamine (3 microM) was superfused on the dopaminergic neurons prior and during the application of cocaine, the DA-uptake blocker was no longer able to potentiate the outward response caused by the superfusion of DA. Taken together, these data suggest that: (i) amphetamine and cocaine interact with the DA transporter to produce distinct actions which under certain circumstances can compete with each other; (ii) the amphetamine-induced release of DA from the somata and dendrites of the dopaminergic cells is, at least in part, related to the reverse operation of the DA transporter and is not dependent on the integrity of the vesicular content of the catecholamine.

Adrenergic Uptake Inhibitors↗
PubMed1999

Amphetamine-induced glutamate efflux in the rat ventral tegmental area is prevented by MK-801, SCH 23390, and ibotenic acid lesions of the prefrontal cortex.

We showed previously that amphetamine challenge produces a delayed increase in glutamate efflux in the ventral tegmental area of both naive and chronic amphetamine-treated rats. The present study examined the mechanisms underlying this response. The NMDA receptor antagonist MK-801 (0.1 mg/kg, i.p.) or the D1 dopamine receptor antagonist SCH 23390 (0.1 mg/kg, i.p.), given 30 min before acute amphetamine (5 mg/kg, i.p.), prevented amphetamine-induced glutamate efflux. Neither antagonist by itself altered glutamate efflux. Ibotenic acid lesions of the prefrontal cortex similarly prevented amphetamine-induced glutamate efflux, while producing a trend toward decreased basal glutamate levels (82.8% of sham group). Previous work has shown that the doses of NMDA and D1 receptor antagonists used in this study prevent the induction of behavioral sensitization when coadministered repeatedly with amphetamine, and that identical prefrontal cortex lesions performed before repeated amphetamine prevent the induction of ambulatory sensitization. Thus, treatments that prevent acute amphetamine from elevating glutamate efflux in the ventral tegmental area also prevent repeated amphetamine from eliciting behavioral sensitization. These findings suggest that repeated elevation of glutamate levels during a chronic amphetamine regimen may contribute to the cascade of neuroadaptations within the ventral tegmental area that enables the induction of sensitization.

Amphetamine↗
PubMed1996

Adrenocortical suppression blocks the memory-enhancing effects of amphetamine and epinephrine.

This study examined glucocorticoid-adrenergic interactions in modulating acquisition and memory storage for inhibitory avoidance training. Systemically (s.c.) administered amphetamine (1 mg/kg), but not epinephrine (0.1 mg/kg) or the peripherally acting amphetamine derivative 4-OH amphetamine (2 mg/kg), given to rats shortly before training facilitated acquisition performance in a continuous multiple-trial inhibitory avoidance (CMIA) task. Adrenocortical suppression with the 11beta-hydroxylase inhibitor metyrapone (50 mg/kg; s.c.), given to rats 90 min before training, did not block the effect of amphetamine and did not affect acquisition performance of otherwise untreated animals. Retention of CMIA and one-trial inhibitory avoidance was enhanced by either pre- or posttraining injections of amphetamine as well as 4-OH amphetamine and epinephrine. The finding that injections of amphetamine and epinephrine have comparable effects on memory is consistent with the view that amphetamine may modulate memory storage, at least in part, by inducing the release of epinephrine from the adrenal medulla. Metyrapone pretreatment blocked the memory-enhancing effects of amphetamine, 4-OH amphetamine, and epinephrine but did not affect retention performance of otherwise untreated animals. Posttraining injections of different doses of epinephrine (ranging from 0.0001 to 1.0 mg/kg) produced a dose-dependent memory enhancement for inhibitory avoidance training and metyrapone blocked the memory-enhancing effects of all these doses. These findings provide further evidence that the sympathoadrenal and adrenocortical systems are intimately coupled during processes of memory storage.

Adrenal Cortex↗
PubMedDate not supplied

Quinidine inhibits in vivo metabolism of amphetamine in rats: impact upon correlation between GC/MS and immunoassay findings in rat urine.

Amphetamine is metabolized by cytochrome P-450 (P450) to p-hydroxyamphetamine and phenylacetone in mammalian species. P450 metabolism is affected by genetic polymorphisms and by xenobiotic interactions in an isozyme-specific fashion. Little is known concerning the isozyme selectivity of amphetamine metabolism. Quinidine selectively inhibits the debrisoquine-specific isozyme (P450db) which displays genetic polymorphism in humans and rats. We now report the effect of quinidine on the metabolism of amphetamine to p-hydroxyamphetamine in vivo. At 0 h male Lewis rats received (po): no treatment (I), 80 mg quinidine/kg in 50% ethanol (II), or 50% ethanol (III), followed at 2 h by 15 mg d-amphetamine sulfate/kg (po). Urine specimens were collected and pooled at 0, 24, and 48 h. Amphetamine and p-hydroxyamphetamine concentrations were determined using a new GC/MS method for simultaneous quantitation. The ethanol vehicle-control (III) had no significant effect on amphetamine metabolism. Quinidine pretreatment (II) resulted in a significant decrease in the excretion of p-hydroxyamphetamine at 24 and 48 h to 7.2 and 24.1% of the vehicle-control levels, respectively, accompanied by a significant increase in amphetamine excretion between 24 and 48 h to 542% of the control. These data show that quinidine inhibits in vivo metabolism of amphetamine in rats and suggest that amphetamine metabolism may, in part, be mediated by an isozyme of P450 which displays genetic polymorphism. The inhibition of amphetamine metabolism results in an increased ratio of parent drug to metabolite concentration (metabolic ratio) in the urine, which mimics the effect of genetic polymorphisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗
PubMed1999

Enhanced acetylcholine release in striatum after chronic amphetamine is NMDA-dependent.

Behavioral sensitization to chronic amphetamine develops in parallel with an enhancement of amphetamine-stimulated efflux of acetylcholine (ACh) in striatum. The present study investigated the role of NMDA receptors in the latter phenomenon. Rats were treated with either saline (1.0 ml/kg, i.p.) or amphetamine (4.0 mg/kg, i.p., b.i.d.) for 12 days followed by a withdrawal period of 2-3 weeks. In vivo microdialysis was employed to measure striatal ACh efflux. Amphetamine challenge (4.0 mg/kg, i.p.) evoked a significant increase in striatal ACh efflux in rats withdrawn from chronic amphetamine while having no significant effect on ACh efflux in saline-pretreated rats. Inclusion of the NMDA receptor antagonist (+/-)-2-amino-5-phoshonopentanoic acid (APV; 100 microM) in the perfusion solution blocked the amphetamine-induced increase in striatal ACh efflux observed in amphetamine-pretreated rats. In saline-pretreated animals, the presence of APV had no apparent effect on the profile of striatal ACh efflux following amphetamine challenge. Thus, the stimulatory effect of amphetamine challenge on striatal ACh efflux that selectively is observed in animals withdrawn from chronic amphetamine is dependent upon NMDA receptor activation.

Acetylcholine↗
PubMed1973

Attenuation of amphetamine-induced motor stimulation and stereotypy by 6-hydroxydopamine in the rat.

1. In accord with previous reports, intraventricular administration of 6-hydroxydopamine (250 mug) to rats did not influence spontaneous locomotor activity. Neither was the stereotyped behaviour seen after high doses of (+)-amphetamine (5 mg/kg) changed by this treatment. Increases in motor activity induced by (+)-amphetamine (0.5 and 1.0 mg/kg) were significantly reduced after 6-hydroxydopamine.2. When 6-hydroxydopamine (250 mug) was administered to tranylcypromine (5 mg/kg) pretreated animals, spontaneous activity was significantly reduced. The stimulant effects of (+)-amphetamine (0.5 and 1.0 mg/kg) were completely abolished and amphetamine stereotypy (5.0 mg/kg) was absent or reduced after this treatment.3. Bilateral injections of 6-hydroxydopamine (10 mug) into the substantia nigra abolished the more pronounced features of amphetamine stereotypy. However, although significantly reduced, amphetamine-induced locomotor stimulation was observed in these animals. Spontaneous activity was also reduced.4. These observations suggest that dopaminergic nigro-striatal neurones mediate some of the stimulant effects of amphetamine as well as being of critical importance in amphetamine-induced stereotypy. However, other catecholaminergic neurones also appear to be involved in amphetamine motor stimulation. The results are consistent with the view that amphetamine exerts its behavioural effects indirectly through its action on brain catecholamines.

Amphetamine↗
PubMed1994

Differential action of (+)-amphetamine on electrically evoked dopamine overflow in rat brain slices containing corpus striatum and nucleus accumbens.

1. The effects of (+)-amphetamine on electrically evoked dopamine overflow were examined in the rat brain slice containing either anterior caudate putamen (aCPu) or nucleus accumbens (NAc), by fast cyclic voltammetry. 2. (+)-Amphetamine (1 microM) caused a time-dependent increase in the extracellular concentration of dopamine ([dopamine]ex) due to displacement of dopamine from terminal sites. After a 40 min superfusion, [dopamine]ex in the aCPu was 0.617 +/- 0.117 microM and in the NAc was 0.270 +/- 0.04 microM. Pretreatment with (-)-sulpiride (1 microM) did not affect this action of (+)-amphetamine. 3. (+)-Amphetamine (1 microM) exhibited a complex and time-dependent effect on electrically stimulated dopamine overflow, evoked by 1p, 4p/10 Hz and 20p/20 Hz. 4. In the aCPu, (+)-amphetamine (1 microM) resulted in attenuation of dopamine overflow due to 1p and 4p/10 Hz but potentiation of dopamine overflow to 20p/20 Hz. (-)-Sulpiride (1 microM) prior to (+)-amphetamine (1 microM) reversed the attenuation of dopamine overflow evoked by 1p and 4p/10 Hz but had no significant effect on dopamine overflow evoked by 20p/20 Hz. 5. (+)-Amphetamine (1 microM) potentiated dopamine overflow in the NAc to all three stimuli. (-)-Sulpiride (1 microM) prior to (+)-amphetamine (1 microM), resulted initially, in a further potentiation of overflow, followed by a time-dependent attenuation of dopamine overflow to all three stimuli. 6. t1/2, the rate of removal of [dopamine]ex following electrical stimulation was not significantly different in the aCPu and NAc for any of the stimulation conditions. After a 40 min superfusion with (+)-amphetamine (1 MicroM), t1/2 for ip, 4p/10 Hz and 20p/20 Hz was significantly increased in both the aCPuand NAc, the increase in t1/2 being significantly greater in the aCPu than in the NAc.7. In conclusion, this study indicates that the dopamine displacement and uptake inhibitory actions of(+ )-amphetamine result in complex and differential effects on electrically evoked dopamine overflow in the aCPu and NAc.

Amphetamine↗
PubMed1991

Amphetamine promotes recovery from sensory-motor integration deficit after thrombotic infarction of the primary somatosensory rat cortex.

The present studies were undertaken to examine 1) whether d-amphetamine sulfate administered to rats well after thrombotic infarction of the vibrissal cortical barrel-field within the primary somatosensory cortex affected the rate and completeness of behavioral recovery and 2) whether a dose-response relation exists between d-amphetamine sulfate dose and recovery of function. In a learning task requiring sensory-motor integration, 41 rats were trained to perform a motor response in a T-maze consequent to the detection of a vibrissal deflection cue. Once training was complete, unilateral (n = 29) or sham (n = 12) infarction was produced by a noninvasive photochemical technique. After infarction, T-maze performance was assessed repeatedly in rats receiving 2 (n = 10) or 4 (n = 10) mg/kg d-amphetamine sulfate or saline (n = 9) 24 hours prior to testing on days 4, 6, 9, and 11. The sham-operated control rats received d-amphetamine sulfate (n = 7) or no injections (n = 5). All three infarcted groups displayed a reliable and sustained behavioral deficit in performance that was not present in the sham-operated control animals. Although the performance of each infarcted group improved over the testing sessions after the first injection, the amphetamine-treated groups improved at a faster rate than the saline-injected group. The results further demonstrated a dose-response effect, with the 4 mg/kg amphetamine group recovering to within preinfarction levels 6-8 days earlier than the 2 mg/kg amphetamine and saline-injected groups. Moreover, both amphetamine-treated groups recovered more completely than the saline-injected group. Quantification of the chronic infarct area revealed no differences among the amphetamine-treated and saline-injected groups. These data provide further evidence of the facilitatory effect of d-amphetamine sulfate on recovery from brain injury and extend this effect to the enhancement of recovery subsequent to thrombotic infarction of the primary somatosensory cortex.

Amphetamine↗
PubMed1975

Blood pressure and heart rate responses evoked by d- and l-amphetamine in the pithed rat preparation.

Isomers of amphetamine were tested for their ability to evoke changes in the spontaneous motor behavior of rats. d-Amphetamine was effective within the dose range of 0.2 to 2.0 mg/kg; l-amphetamine was effective within the range of 1.0 to 10.0 mg/kg. Both d- and l-amphetamine were also compared for their pressor and tachycardic activity in pithed rats. The doses of amphetamine tested (0.1-10.0 mg/kg) were identical to those which produced changes in behavior. d-Amphetamine was approximately 5-fold more potent than l-amphetamine in evoking pressor responses and approximately 3-fold more potent in evoking tachycardic responses. The two isomers differed little in their ability to block norepinephrine uptake into heart. The ID50 values were; d-amphetamine 0.7 mg/kg; l-amphetamine, 1.2 mg/kg. Cocaine, which also blocked norepinephrine uptake into heart (ID50 = 3.0 mg/kg), lacked significant pressor or tachycardic activity in pithed, adrenalectomized animals. The inability of cocaine to evoke responses was related to the marked reduction in norepinephrine turnover and release in pithed animals. It was concluded that differences in potency between d- and l-amphetamine cannot be explained on the basis of blockade of norepinephrine uptake. The difference may relate to evoked release of amine.

Adrenal Glands↗