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Biomedical subjects

R Maldonado

Publications and source records attributed to R Maldonado.

At least 73 records · Page 4Linked to original sources
PubMed1995

Weak tolerance to the antinociceptive effect induced by the association of a peptidase inhibitor and a CCKB receptor antagonist.

We have recently shown that CCKB receptor antagonists such as PD-134,308, 4-([2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[tricyclo[3.3.1.1]dec - 2-yloxy)carbonyl]amino]propyl]amino]-1-phenylethyl]amino)-4-oxo[R- (R*,R*)]-butanoate-N-methyl-D-glucamine, are able to strongly potentiate antinociception induced by endogenous enkephalins, protected from degrading enzymes by the mixed inhibitor RB 101, N-[(R,S)-2-benzyl-3[(S)-(2-amino-4- methylthio)butyldithio]-1-oxopropyl)-L-phenylalanine benzyl ester, at both spinal and supraspinal levels. In this study, the duration of this facilitatory response and the possible development of tolerance to this synergistic effect were investigated in the rat tail-flick test after acute and chronic treatment with PD-134,308 and RB 101. PD-134,308 facilitated and prolonged the antinociceptive responses induced by RB 101 (20 mg/kg, i.v.). The duration of the effect induced by PD-134,308 was also investigated by injecting this compound at different times before RB 101 administration. In the case of the tail-flick test, the improvement of RB 101 antinociceptive response was still significant 6 h after PD-134,308 (3 mg/kg, i.p.), whereas in the hot-plate test, this enhancement was only effective for 3 h after CCKB receptor antagonist administration. In the case of a repeated administration of RB 101, the potentiation induced by PD-134,308 on the antinociceptive effect produced by the first injection of RB 101 (20 mg/kg, i.v.), was found almost identical after a second administration of RB 101 performed 190 min later. Chronic administration of RB 101 (20 mg/kg, i.v.) plus PD-134,308 (3 mg/kg, i.p.) administered for 5 days both once or twice per day, did not induce the development of tolerance to antinociception at the peak effect time. However, a decrease in the duration of the antinociceptive response was observed. These results indicate that the potent and long-lasting antinociceptive response induced by the coadministration of the peptidase inhibitor and the CCKB receptor antagonist could have interesting perspectives in the clinical treatment of pain.

Analgesics↗
PubMed1995

Protein kinases in the locus coeruleus and periaqueductal gray matter are involved in the expression of opiate withdrawal.

The aim of this study was to evaluate the role played in the behavioral expression of morphine withdrawal syndrome by protein kinases in the locus coeruleus and the periaqueductal gray matter. Two different families of specific protein kinases have been investigated: serine/threonine and tyrosine kinases. Rats were implanted with cannulas into both the lateral ventricle and the locus coeruleus or the periaqueductal gray matter. Physical dependence was induced by chronic peripheral administration of morphine (from 7 to 30 mg/kg) and withdrawal syndrome was precipitated by injection of naloxone (2 micrograms) into the lateral ventricle. The administration of the serine/threonine kinase inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, H7 (1, 3, 10, and 30 nmol per side) into the locus coeruleus induced a strong attenuation of morphine withdrawal behavior. Signs related to the motor component of abstinence, such as jumping, rearing, and hyperactivity, were the most severely reduced. However, this effect was not dose-dependent, and the response was almost the same with all the doses used. A similar attenuation was observed after the injection of H7 (1, 3, and 10 nmol per side) into the periaqueductal gray matter, but in this case motor signs were less strongly reduced and a larger number of signs were modified, mainly when using the highest dose. The administration of the tyrosine kinase inhibitor 2-hydroxy-5-[N(2,5-dihydroxyphenyl)methyl]amino]-benzoic acid 3-phenylpropyl ester, KB23 (0.3, 1, and 3 nmol per side) into the locus coeruleus or the periaqueductal gray matter had no effect on the withdrawal syndrome behavior, except on teeth chattering. These results suggest that in the locus coeruleus and in the periaqueductal gray matter, serine/threonine kinases are implicated in the behavioral expression of morphine abstinence. In these brain structures, tyrosine kinases appear not to be involved.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Opposite role of CCKA and CCKB receptors in the modulation of endogenous enkephalin antidepressant-like effects.

Systemic administration of RB 101, a complete inhibitor of the enkephalin degrading enzymes, has been reported to induce naltrindole-reversed antidepressant-like effects in the conditioned suppression of motility (CSM) test in mice. The selective CCKB antagonist L-365,260 also elicits the same naltrindole-blocked responses on CSM. The aim of this study was therefore to investigate the possible modulation of RB 101 induced behavioral responses by activation or blockade of CCK receptors. Thus, the effects induced by RB 101 administered alone or associated with an ineffective dose of a selective CCKB agonist (BC 264), a CCKB antagonist (L-365,260) or a CCKA antagonist (L-364,718), were evaluated on the CSM in mice. RB 101 alone decreased the stress-induced loss of motility, as previously reported. The antidepressant-like effect of RB 101 was potentiated by L-365,260, and suppressed by BC 264 and to a lesser extent by L-364,718. The facilitatory effect induced by L-365,260 on RB 101 responses was blocked by the delta selective antagonist naltrindole. All these effects occurred only in shocked animals. The present results suggest that the activation of CCKA and CCKB receptors by endogenous CCK, could play an opposite role in the control of behavioral responses induced by endogenous enkephalins. Delta opioid receptors seem to be selectively involved in this interaction.

Analgesics↗
PubMed1995

Implication of endogenous opioid system in the learned helplessness model of depression.

The involvement of opioid system on the learned helplessness model of depression was investigated. Animals preexposed to inescapable shocks were treated with either Met-enkephalin, Leu-enkephalin, morphine, imipramine, naloxone, RB 38A (a mixed inhibitor of enkephalin degrading enzymes), or RB 38B (a selective inhibitor of neutral endopeptidase EC 3.4.24.11). Stimulation of opioid system by either opioid agonists or enkephalin catabolism inhibitors reversed the escape deficit induced by shock pretreatment. In contrast, administration of naloxone potentiated the effect of inescapable shocks. Imipramine reduced the number of escape failures in this test, and this effect was antagonized by naloxone. These results point to the involvement of the endogenous opioid system in this model of depression.

Animals↗
PubMed1995

Study of the mechanisms involved in behavioral changes induced by flunitrazepam in morphine withdrawal.

1. The attenuation of morphine withdrawal syndrome by acute benzodiazepine administration has been well documented. However, the pharmacological mechanisms implicated in this effect remain unclear. 2. In this study, the possible participation of noradrenergic, serotonergic and benzodiazepine receptors on flunitrazepam-modified morphine withdrawal syndrome was investigated in mice. Flunitrazepam was associated to the noradrenergic antagonists prazosin (1 mg/kg) and propranolol (0.5 mg/kg), the serotonergic agents ritanserine (1 mg/kg) and p-chloro phenylalanine (600 mg/kg), the benzodiazepine antagonist flumazenil (10 mg/kg), and the benzodiazepine partial inverse agonist Ro 15-4513 (5 mg/kg). 3. The decrease in jumping behavior-induced by flunitrazepam was potentiated by prazosin, while ritanserine, flumazenil and Ro 15-4513 blocked this effect. 4. Flunitrazepam-induced increase on wet dog shake frequency was partially reduced by flumazenil, and strongly antagonized by ritanserine and Ro 15-4513. 5. Noradrenergic and serotonergic systems seem to be primarily implicated in the changes induced on jumping and wet dog shakes respectively. These modifications are induced through the activation of the benzodiazepine receptors.

Animals↗
PubMed1995

Inhibition of morphine withdrawal by the association of RB 101, an inhibitor of enkephalin catabolism, and the CCKB antagonist PD-134,308.

1. The effects induced in rats on naloxone-precipitated morphine withdrawal syndrome by the new mixed inhibitor of enkephalin catabolism able to cross the blood-brain barrier RB 101 (N-((R,S)-2-benzyl-3[(S)(2-amino-4-methylthio)butyl dithio]-1-ox-opropyl-L-phenylalanine benzyl ester) given alone or associated with the selective CCKB antagonist, PD-134,308, were investigated. 2. The systemic administration of RB 101 (5, 10 and 20 mg kg-1, i.v.) elicited a significant decrease in 8 of the 14 withdrawal signs evaluated. PD-134,308 (3 mg kg-1, i.p.) did not modify the expression of morphine abstinence when given alone, but induced a strong facilitation of RB 101 responses (12 of 14 withdrawal signs were decreased). This potentiation was particularly intense in peripherally mediated withdrawal signs. 3. In order to clarify the biochemical mechanisms implicated in these responses, the effects induced by the association of RB 101 and PD-134,308 on the occupation of brain opioid receptors by endogenous enkephalins were also investigated in mice. PD-134,308, as well as RB 101, inhibited [3H]-diprenorphine binding to opioid receptors. These results suggest that an increase in endogenous enkephalin levels induced by PD-134,308 could participate in the facilitation of RB 101 behavioural responses. 4. RB 101 has a promising potential role in the management of the opiate withdrawal syndrome. CCKB antagonists, such as PD-134,308 may be useful in potentiating this anti-withdrawal effect.

Analgesics↗
PubMed1995

Phosphorus-containing peptides as mixed inhibitors of endopeptidase 3.4.24.15 and 3.4.24.16: effect on neurotensin degradation in vitro and in vivo.

1. We have examined several phosphorus-containing peptides as potential mixed inhibitors of two neurotensin-degrading zinc metallopeptidases, endopeptidase 3.4.24.15 and endopeptidase 3.4.24.16. 2. Among a series of 13 phosphonamide peptides, N-(2-(2-naphtyl)ethylphosphonyl-glycyl-prolyl-norleucine (phosphodiepryl 08) was found to inhibit potently the hydrolysis of neurotensin by purified endopeptidase 3.4.24.15 and 3.4.24.16 with an identical Ki value of 0.4 nM. 3. Phosphodiepryl 08 displayed a strong selectivity towards the two peptidases since it failed to inhibit several other zinc-containing peptidases such as endopeptidase 3.4.24.11, angiotensin-converting enzyme, aminopeptidase M, leucine aminopeptidase and carboxypeptidases A and B. 4. The protective effect of phosphodiepryl 08 on neurotensin degradation was examined in vitro and in vivo in central and peripheral bioassays. 5. Phosphodiepryl 08 virtually abolished neurotensin degradation by 4-day-old plated pure cultured neurones from mouse embryos and greatly potentiated neurotensin-induced antinociception in the mouse hot plate test. 6. In the periphery, phosphodiepryl 08 inhibited neurotensin degradation by membranes prepared from isolated longitudinal smooth muscle of guinea-pig ileum and greatly potentiated the neurotensin-induced contraction of the same longitudinal smooth muscle preparation. 7. Our study indicates that phosphodiepryl 08 behaves as a potent and selective mixed inhibitor of endopeptidase 3.4.24.15 and 3.4.24.16 and can be used as a powerful agent to prevent neurotensin degradation, in vitro and in vivo, in central and peripheral assays.

Animals↗
PubMed1994

Chronic morphine administration causes region-specific increase of brain type VIII adenylyl cyclase mRNA.

The up-regulation of the cyclic AMP system and enhanced phosphorylation of protein substrates after either sudden interruption of chronic opioid treatment or antagonist administration has been proposed to account for the various behavioral responses observed during withdrawal. Using in situ hybridization histochemistry, we show here for the first time that type VIII adenylyl cyclase mRNA is selectively increased, as early as 12 h after morphine treatment in the locus coeruleus and the amygdala, two brain regions suggested to be important in morphine dependence expression. Moreover, the time course of morphine-induced changes in type VIII adenylyl cyclase mRNA in locus coeruleus is related to the incidence of jumping, the most important sign of morphine withdrawal in mice. In addition, the overexpression of type VIII adenylyl cyclase mRNA in thalamic nuclei could add to morphine tolerance. These findings offer a strong support, at the molecular level, for an altered regulation of the cyclic AMP system in opiate tolerance and dependence. The present measure relates only to type VIII adenylyl cyclase mRNA and similar tests with other cyclases are needed to explore fully this relationship.

Adenylyl Cyclases↗
PubMed1994

Regulation of rat glomerular epithelial cell proteoglycans by high-glucose medium.

In diabetic nephropathy the heparan sulfate proteoglycan (HSPG) content of the glomerular basement membrane (GBM) is reduced but the cellular mechanisms involved have not been studied. Glomerular epithelial cells (GEC) are thought to be the source of HSPG present in the GBM. In this study we examined if proteoglycan metabolism of the rat GEC in culture is dysregulated in a metabolic environment simulating diabetes. Following incubation for 8 days with a serum-supplemented medium containing 30 mM glucose and no added insulin, a significant increase in the overall synthesis of 35SO4-labeled molecules by the GEC was seen compared to control monolayers incubated with medium containing 5 mM glucose and insulin. Ion exchange chromatography revealed that 30 mM glucose did not alter the anionic charge density of proteoglycans, but significantly increased the amount of 35S-labeled low-anionic macromolecules in the medium; mannitol induced similar changes. Sepharose CL-4B chromatography, glycosaminoglycan analysis and immunoprecipitation of control cell layer proteoglycans demonstrated the presence of HSPG of hydrodynamic size, Kav 0.4, resembling rat GBM HSPG in size and antigenic nature. Incubation of GEC with 30 mM glucose resulted in a significant reduction (58%) in this HSPG species, an effect not seen with equimolar mannitol. Additionally, 30 mM glucose induced a significant increment in synthesis of a small HS species (Kav 0.71 on Sepharose CL-4B column) present in the cell layer. Our findings suggest that both osmotic and nonosmotic mechanisms are operative in dysregulation of glycopeptide metabolism by high-glucose medium and that reduced synthesis by the GEC may contribute to decreased content of GBM HSPG in diabetic nephropathy.

Animals↗
PubMed1994

Effects induced by BC 264, a selective agonist of CCK-B receptors, on morphine-dependent rats.

The aim of this study was to investigate the possible interaction between neuronal cholecystokinin (CCK) and opiate dependence. Rats were made dependent to morphine and the ability of cholecystokinin-octapeptide (CCK-8) and Tyr(SO3H)-gNle-mGly-Trp-(NMe)Nle-Asp-Phe-NH2 (BC 264), a selective agonist of CCK-B receptors, to induce signs of morphine withdrawal after ICV injection was tested. Behavioral responses were compared to those occurring during the naloxone-precipitated morphine withdrawal syndrome. In contrast to naloxone, CCK-8 (0.1, 1, and 10 micrograms, ICV) did not precipitate any sign of withdrawal. BC 264 (0.1, 1, and 10 micrograms, ICV) induced a strong hyperlocomotion and wet dog shakes in morphine-dependent rats, the latter effect also observed in nondependent animals. In rats receiving acute morphine, BC 264 induced an opposite effect (i.e., blockade of morphine-induced hyperactivity). Taken together, these results suggest that CCK plays only a minor role in the expression of morphine physical dependence.

Amino Acid Sequence↗
PubMed1994

Participation of opioid and monoaminergic mechanisms on the antinociceptive effect induced by tricyclic antidepressants in two behavioural pain tests in mice.

1. Various clinical and experimental reports indicate that tricyclic antidepressant drugs are specially useful in the treatment of chronic and acute pain conditions. The present work was aimed to study the mechanisms implicated in the antinociceptive response induced by these antidepressants on different experimental models of pain in mice, and particularly the role played by noradrenergic, serotonergic and opioidergic influences. 2. Electrical stimulation of the tail and formalin tests were used to evaluate pain perception in mice acutely treated with different antidepressants (imipramine, desipramine, amitriptyline, nortriptyline, clomipramine and desmethylclomipramine). Antinociceptive responses were more potent in formalin test than in tail electrical stimulation test. 3. These antinociceptive effects were inhibited by naloxone (2 mg/Kg, i.p.), alpha-methyl-p-tyrosine (200 mg/Kg) and p-chlorophenylalanine (600 mg/Kg). Naloxone elicited the same effectivity to inhibit antinociceptive responses induced by tricyclic antidepressants in both tail electrical stimulation and formalin tests. alpha-methyl-p-tyrosine and p-chlorophenylalanine were more effective on antinociceptive responses induced on formalin than in tail electrical stimulation test. 4. These results suggest that tricyclic antidepressants produce antinociception partly via the participation of the endogenous opioid system and partly by further activating noradrenergic and serotonergic pathways. Moreover, the analgesic responses and the mechanisms implicated were dependent of the analgesimeter test used.

Analgesics↗
PubMed1994

Antinociceptive response induced by mixed inhibitors of enkephalin catabolism in peripheral inflammation.

RB101 (N-((R,S)-2-benzyl-3[(S)(2-amino-4-methylthio)butyl dithio]-1-ox-opropyl)-L-phenylalanine benzyl ester) is a recently developed full inhibitor of the enkephalin-catabolizing enzymes able to cross the blood-brain barrier, whereas RB38A ((R)-3-(N-hydroxycarboxamido-2-benzylpropanoyl)-L-phenylalanine) is as potent as RB101 but almost unable to enter the brain. In this study, we have investigated the effects of systemic administration of morphine, RB101 and RB38A on nociception induced by pressure on inflamed peripheral tissues. Antinociceptive test was performed between 4 and 5 days after injection into the rat left hindpaw of Freund's complete adjuvant to produce localized inflammation. Morphine (1, 2 and 4 mg/kg, i.v.) induced antinociception in inflamed paws at all the doses used, and only at the highest dose in non-inflamed paws. RB101 (10 and 20 mg/kg, i.v.) induced an antinociceptive response only in the inflamed paws. RB38A, also induced an antinociceptive effect in the inflamed paws, but only at the highest dose (20 mg/kg, i.v.). The responses induced by morphine and the inhibitors of enkephalin catabolism were antagonized by the systemic administration of naloxone (1 mg/kg) or methylnaloxonium (2 mg/kg) which acts essentially outside the brain. Central injection (i.c.v.) of methylnaloxonium (2 micrograms) blocked the effect of morphine only in non-inflamed paws, and slightly decreased the response induced by RB101 on inflamed paws. These results indicate that the endogenous opioid peptides, probably enkephalins, are important in the peripheral control of nociception from inflamed tissues.

Analgesics↗
PubMed1994

Changes of ploidy during the Azotobacter vinelandii growth cycle.

The size of the Azotobacter vinelandii chromosome is approximately 4,700 kb, as calculated by pulsed-field electrophoretic separation of fragments digested with the rarely cutting endonucleases SpeI and SwaI. Surveys of DNA content per cell by flow cytometry indicated the existence of ploidy changes during the A. vinelandii growth cycle in rich medium. Early-exponential-phase cells have a ploidy level similar to that of Escherichia coli or Salmonella typhimurium (probably ca. four chromosomes per cell), but a continuous increase of DNA content per cell is observed during growth. Late-exponential-phase cells may contain > 40 chromosomes per cell, while cells in the early stationary stage may contain > 80 chromosomes per cell. In late-stationary-phase cultures, the DNA content per cell is even higher, probably over 100 chromosome equivalents per cell. A dramatic change is observed in old stationary-phase cultures, when the population of highly polyploid bacteria segregates cells with low ploidy. The DNA content of the latter cells resembles that of cysts, suggesting that the process may reflect the onset of cyst differentiation. Cells with low ploidy are also formed when old stationary-phase cultures are diluted into fresh medium. Addition of rifampin to exponential-phase cultures causes a rapid increase in DNA content, indicating that A. vinelandii initiates multiple rounds of chromosome replication per cell division. Growth in minimal medium does not result in the spectacular changes of ploidy observed during rapid growth; this observation suggests that the polyploidy of A. vinelandii may not exist outside the laboratory.

Azotobacter vinelandii↗
PubMed1994

Cholecystokinin B antagonists strongly potentiate antinociception mediated by endogenous enkephalins.

The effects of pretreatment with the selective cholecystokinin (CCK) B antagonists (3R-(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1, 4-benzodiazepin-3-yl)-N1-(3-methylphenyl urea (L-365,260), 4-([2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2-[[tricyclo[3.3, 1.1(3.7)]dec-2-yloxy)carbonyl]amino]propyl]amino]-1-phenylethyl] amin)-4-oxo-[R-(R*,R*)]butanoate-N-methyl-D-glucamine (PD-134,308) and N-(2-adamantyloxycarbonyl)-D-alpha-methyltryptophanyl-[N-(2- (4-chlorophenyl)ethyl)]glycine (RB 211), on the naloxone-reversible, antinociceptive responses induced by systemic (i.v.) administration of the complete inhibitor of the enkephalin-catabolizing enzymes, N-((R,S,)-2-benzyl-3[(S)-(2-amino-4-methylthio)butyldithio]-1- oxopropyl)-L-phenylalanine benzyl ester (RB 101), were determined in rat tail-flick and mouse hot-plate tests. L-365,260 (0.12, 0.25 and 0.5 mg/kg s.c.), PD-134,308 (0.3, 1 and 3 mg/kg i.p.) and RB 211 (0.5, 1 and 1.5 mg/kg i.p.) strongly potentiated the antinociceptive effects induced by RB 101 in the rat tail-flick test, in which spinal control of nociception is predominant. Thus, the antinociception observed after the association of L-365,260 (0.5 mg/kg), RB 211 (1.5 mg/kg) or PD-134,308 (3 mg/kg) with RB 101 (5 mg/kg) was, respectively, 300, 500 and 800% higher than that observed with RB 101 given alone. This facilitatory effect was partially blocked by the administration of naloxone (1 mg/kg s.c.). Under the same conditions the potentiation of the antinociceptive response produced by morphine (0.1-4 mg/kg s.c.) was inferior to 250%. In the mouse hot-plate test, L-365,260 (0.02 and 0.1 mg/kg i.p.) and PD-134,308 (0.3, 1 and 3 mg/kg i.p.) also enhanced endogenous enkephalin induced antiociception, but this potentiating effect, completely reversed by administration of naloxone (0.1 mg/kg s.c.), was about 2 times less effective than in the tail-flick assay. The present findings demonstrate an opposing physiological role of endogenous CCK, acting on CCK B receptors, and opioid peptides in the control of pain perception at both spinal and supraspinal levels. These results could have important clinical applications because a combination of a CCK B antagonist and RB 101, which has been showed to be almost devoid of morphine side effects, would increase the overall antinociceptive efficacy into a range that will be more clinically useful.

Adamantane↗
PubMed1993

Cholecystokinin-A but not cholecystokinin-B receptor stimulation induces endogenous opioid-dependent antinociceptive effects in the hot plate test in mice.

The effects of intracerebroventricular administration of the cholecystokinin (CCK) analogue, BDNL, and the selective CCK-B agonist, BC 264, were determined using the hot plate test in mice. BDNL (0.2 nmol and 0.5 nmol) increased the jump and the paw lick latencies. These effects were blocked by the CCK-A antagonist MK-329 (0.02 mg/kg), supporting the involvement of CCK-A receptors in CCK-induced analgesia. In contrast, the selective CCK-B agonist BC 264 produced, at one dose (2.5 nmol), a slight decrease in the lick latency that was only antagonized by the CCK-B antagonist. Naloxone, but not naltrindole, antagonized BDNL-induced analgesia. The results suggest that activation of CCK-A receptors by BDNL leads to antinociceptive responses indirectly mediated by stimulation of mu-opioid receptors by endogenous enkephalins.

Animals↗
PubMed1993

Neurotensin injected into the nucleus accumbens blocks the psychostimulant effects of cocaine but does not attenuate cocaine self-administration in the rat.

The neuropeptide neurotensin (NT) has been shown to modulate mesolimbic dopaminergic activity. Neurotensin injected into the VTA produces motor stimulation and release of dopamine in the nucleus accumbens. In contrast, when neurotensin is administered into the nucleus accumbens, it produces neuroleptic-like effects such as attenuation of the locomotor activity elicited by psychostimulants. In the present study, the hypothesis that neurotensin injected into the nucleus accumbens might modulate the psychostimulant and reinforcing actions of cocaine was tested. In experiment one, rats were trained to self-administer cocaine intravenously on an FR5 schedule of reinforcement. Following the establishment of baseline responding, rats were implanted with bilateral cannulae in the nucleus accumbens. One week later, rats were injected into the nucleus accumbens with various doses of neurotensin (4.2, 8.4 and 16.7 micrograms, total doses bilaterally) immediately prior to the self-administration session. No significant effects were found with any of the doses of neurotensin tested on the self-administration of cocaine. However, in experiment 2, neurotensin at doses of 4.2 and 16.7 micrograms injected into the nucleus accumbens significantly reduced the locomotor activation induced by an acute injection of cocaine (15 mg/kg i.p.) and a dose of 16.7 micrograms attenuated the locomotor activation induced by amphetamine (0.75 mg/kg i.p.). Thus, neurotensin in the nucleus accumbens appears to specifically modulate the acute locomotor activating properties of cocaine but not cocaine self-administration. Different mechanisms by which NT interacts with dopamine in the nucleus accumbens may provide a means of selectively altering psychostimulant motor actions without affecting psychostimulant reinforcement.

Amphetamine↗