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At least 811 records · Page 45Linked to original sources

PubMed1991

The effect of methamphetamine on serotonin and its metabolite in the suprachiasmatic nucleus: a microdialysis study.

The suprachiasmatic nucleus (SCN) has been identified as a major circadian pacemaker. Methamphetamine has been shown to modify the behavior of circadian rhythms. We detected extracellular serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the SCN in freely moving rats, using a microdialysis method, to investigate biochemical effects of methamphetamine in the SCN. Methamphetamine infusion into the SCN dose-dependently increased extracellular 5-HT and decreased extracellular 5-HIAA.

Animals↗

PubMed1991

The effect of methamphetamine on the release of glutamate from striatal slices.

One postulated role of dopamine in the striatum is to reduce neuronal activity in cortico-striatal glutamergic terminals. We investigated the effects of methamphetamine, which displaces dopamine, on glutamate release from rat striatal slices. Methamphetamine significantly reduced K(+)-stimulated (45 mM) glutamate release. In slices prepared from rats treated 8 days previously with methamphetamine there was enhanced (approximately 200%) release of glutamate. This study demonstrates that dopamine has a modulatory effect on glutamate release in the striatum.

Animals↗

PubMed1995

Scopolamine prevents augmentation of stereotypy induced by chronic methamphetamine treatment.

Cholinergic neurotransmission has been implicated in various forms of neural plasticity such as kindling and learning. We have previously shown that blockade of muscarinic cholinergic receptors prevents the development of locomotor sensitization to methamphetamine. The present study was conducted to examine whether scopolamine, a muscarinic cholinergic antagonist, would also block augmentation of stereotypy induced by chronic methamphetamine (MA) treatment. Rats treated with MA (2.5 mg/kg, SC) for 10 days indicated significantly enhanced stereotyped behavior when tested with MA (2.5 mg/kg) after a 7- to 8- day withdrawal. Pretreatment with scopolamine (3 mg/kg) prior to MA administration prevented the augmentation of stereotypy. Rats treated with scopolamine alone showed no difference in MA-induced stereotypy compared to those treated with saline. Scopolamine methylbromide, a derivative of scopolamine that does not easily cross the blood-brain barrier, had no effect on the augmentation of stereotypy. These results suggest that stimulation of central muscarinic cholinergic receptors plays a role in the development of sensitization to the stereotypy stimulating effect of methamphetamine.

Animals↗

PubMed1994

Methamphetamine exposure during early postnatal development in rats: II. Hypoactivity and altered responses to pharmacological challenge.

Methamphetamine induces neurotransmitter reductions and neurotoxicity at high doses in adult animals, but its effects on early brain development and behavior have received little attention. In this experiment the effects of methamphetamine exposure during a period equivalent to the human third trimester were examined. Rats (Sprague-Dawley CD) were injected subcutaneously with d-methamphetamine (d-MA) (30 mg/kg b.i.d.) early in postnatal development (days 1-10), later (postnatal days 11-20), or with water during both of these periods. Both early and later MA-exposed offspring exhibited reduced locomotor activity. The effect was most evident at 30 days of age and was smaller at 45 and 60 days and only present at these latter ages in males. Only the early MA exposure group showed prolonged suppression of activity in response to a challenge dose of fluoxetine and a persistent deficit in weight while only the later MA exposure group showed attenuated suppression of activity in response to a challenge dose of fluoxetine. Based both on the present data and those in the preceding article, it was concluded that the effects of MA are both long lasting and stage dependent and involve arousal as well as cognitive functions.

Aging↗

PubMed2003

Different glial response to methamphetamine- and methylenedioxymethamphetamine-induced neurotoxicity.

The consequences of the neurotoxic insult induced by 3,4-methylenedioxymethamphetamine (MDMA, an amphetamine derivative with specific action on the serotonergic system) were compared with those of methamphetamine (a derivative with specific action on dopaminergic system) in rats. Both drugs induced a very similar loss of body weight, especially evident 24 h after treatment. Their hyperthermic profile was also very similar and was dependent on ambient temperature, corroborating the thermo-dysregulatory effect of both substances. Methamphetamine (four injections of 10 mg kg(-1) s.c. at 2-h intervals) induced the loss of dopaminergic (35%) but not of serotonergic, terminals in the rat striatum and, simultaneously, a significant increase in striatal peripheral-type benzodiazepine receptor density, pointing to a glial reaction. Evidence for this drug-induced astrogliosis was the increased heat shock protein 27 (HSP27) expression in striatum, cortex and hippocampus. MDMA (20 mg kg(-1) s.c. b.i.d. for 4 days) induced a similar dopaminergic lesion in the striatum 3 days post-treatment, which reversed 4 days later. An important neurotoxic effect on serotonergic terminals was also observed in the cortex, striatum and hippocampus 3 days post-treatment, which partially reversed 4 days later in the striatum and hippocampus. No microglial activation was noticeable at either 3 or 7 days after MDMA treatment. This lack of effect on microglial cells was assessed by [(3)H]PK 11195 binding and OX-6 immunostaining, which were unchanged in the striatum and cortex after MDMA treatment. A non-significant tendency to increase was noted in the hippocampus 3 days after MDMA treatment. Furthermore, in MDMA-treated rats, neither HSP27 expression nor an increase in HSP27 immunoreactivity were detected. This result, together with the lack of increase in glial fibrilliary acidic protein (GFAP) immunoreactivity, indicate no astroglial activation at either 3 or 7 days post-treatment. Without microglial activation, an inflammatory process would not accompany the lesion induced by MDMA. The differences in glial activation between methamphetamine and MDMA observed in the present study could have implications for the prognosis of the injury induced by these drugs.

Animals↗

PubMed2002

Enhancement of N-methyl- D-aspartate receptor-mediated excitatory postsynaptic potentials in the neostriatum after methamphetamine sensitization. An in vitro slice study.

It has been suggested that behavioral methamphetamine sensitization involves changes in cortical excitatory synaptic inputs to neostriatal (Str) projection neurons. To test this, we performed blind whole-cell recording of medium spiny neurons in Str slice preparations. In Str neurons of naive rats, the amplitude of the subcortical white matter stimulation-induced N-methyl- D-aspartate receptor-mediated excitatory postsynaptic potentials (NMDA-EPSPs) was decreased upon hyperpolarization, owing to the voltage-dependent Mg(2+) blockade of NMDA receptor channels. In contrast, the amplitude of the NMDA-EPSPs in Str neurons of rats undergoing methamphetamine withdrawal (MW) did not show the Mg(2+) blockade and was nearly voltage independent over the membrane potential range of -70 to -110 mV. Application of the specific protein kinase C (PKC) activator, phorbol 12, 13- DL-acetate, blocked the voltage-dependent Mg(2+) blockade of NMDA receptor channels in Str neurons of naive rats. Application of the specific activator of cAMP-dependent protein kinase A (PKA), Sp-cAMPS-triethylamine salt, increased the amplitude of the NMDA receptor-mediated EPSPs at the rest but not at hyperpolarized potentials. Coapplication of the PKC and PKA activators yielded NMDA-EPSPs similar to those seen in Str neurons of MW rats. In Str slices of naive rats, tetanic subcortical white matter stimulation induced long-term depression of field potentials. In Str slices treated with the PKC and/or PKA, the same stimulation induced long-term potentiation of field potentials similar to those observed in slices obtained from MW rats. These results suggest that the enhancement of the NMDA receptor-mediated corticostriatal synaptic transmission plays an important role in behavioral methamphetamine sensitization. This enhancement is probably associated with phosphorylation of NMDA receptors mediated by the simultaneous activation of PKC and PKA.

Animals↗

PubMed2005

Isolation rearing or methamphetamine traumatisation induce a "dysconnection" of prefrontal efferents in gerbils: implications for schizophrenia.

A miswiring of prefrontal efferents is generally discussed by the name of "dysconnection" as the anatomical substrate of schizophrenia. Since direct histological confirmation of this hypothesis can hardly be obtained in humans, we used an animal model of schizophrenia to trace prefrontal efferents to distal cortical fields. Mongolian gerbils were intoxicated with a single high dose of methamphetamine on postnatal day 14 and reared in isolation after weaning (day 30). Controls received a saline injection and/or were reared under enriched conditions. Upon reaching adulthood (day 90), biocytin was injected into the medial prefrontal cortex into either deep or superficial laminae. The density of passing fibres and terminal fields in the frontal, parietal and insular cortices was assessed by digital image analysis. Isolation rearing or methamphetamine treatment alone reduced the projections from lamina V/VI to the frontal and from lamina III to the insular cortex, and from both laminae to the parietal cortex. In contrast, isolation rearing of methamphetamine-intoxicated gerbils significantly increased the projections from the deep laminae to the frontal and parietal cortices, compared to isolation-reared controls, with no difference in the efferents from superficial laminae. These results are the first to demonstrate a miswiring of prefrontal efferents in response to adverse systemic influences. They might give a hint at the anatomical basis of "dysconnection" in schizophrenia.

Animals↗

PubMed1999

A single neonatal dose of methamphetamine suppresses dentate granule cell proliferation in adult gerbils which is restored to control values by acute doses of haloperidol.

A single non-invasive dose of methamphetamine (50 mg/kg; i.p.) was administered to neonatal male gerbils (Meriones unguiculatus) aged 14 days. The first objective of the present study was to examine whether this early drug challenge, which has been shown to induce suppressive postnatal maturation of prefrontal dopamine (DA) innervation (Dawirs et al., 1994), interferes with adult granule cell proliferation in the dentate gyrus. Proliferation of granule cells was identified by in-vivo labeling with 5-bromo-2'-desoxyuridine (BrdU). BrdU-labeled granule cell nuclei were identified in consecutive horizontal sections along the mid-septotemporal axis of the hippocampus and light-microscopically quantified 7 days after BrdU-labeling. It was found that a single neonatal dose of methamphetamine was a stimulus strong enough to significantly attenuate adult granule cell proliferation. This effect was clearly lateralized with significant suppression of mitotic activity becoming apparent solely in the left dentate gyrus (-34%). The second objective of the present study was to examine whether acute doses of haloperidol, which have been found to stimulate granule cell proliferation in healthy adult animals (Dawirs et al., 1988), might restore mitotic activity to control values. For that purpose, at the age of postnatal day 90 adult animals which had been challenged with methamphetamine as juveniles received 4 doses of haloperidol (5 mg/kg; i.p.). Proliferation of granule cells was identified by BrdU-labeling. It was found that this neuroleptic treatment acutely restored granule cell proliferation rates to control values. The present results are discussed with regard to (1) factors, regulating mitotic activity in the hippocampus and (2) probable clues they may provide for understanding the neurobiological basis of psychotic behavior.

Aging↗

PubMed1987

Induction of methamphetamine-specific antibody using biodegradable carboxymethyl-chitin.

Induction of a specific antibody for methamphetamine, an antihypnotic drug, has been studied using carboxymethyl-chitin (CM-chitin) as a hapten carrier. The hapten-specific antiserum was induced by only a couple of hypodermal injections every 2 weeks. Inhibition of antigen-antibody complex formation was linearly related to methamphetamine concentration in the range 0.5 to 50 ng/50 microliter when an enzyme-linked immunosorbent assay was performed using an avidin-biotin-peroxidase complex. Little antibody directed against CM-chitin and CM-chitin oligomer was detected. Thus it seems to be advantageous in the hapten-bovine serum albumin system. The specificity of the antibody was high as shown by the use of various methamphetamine analogs.

Animals↗

PubMed1993

Autoradiographic localization of CCK-8 binding sites in the rat brain: effects of chronic methamphetamine administration on these sites.

The effects of chronic methamphetamine (MAP) administration (at a dose of 4 mg/kg for 14 days) on [3H]pCCK-8 binding sites in the rat brain were investigated by an in vitro quantitative receptor autoradiographic technique. The number of [3H]pCCK-8 binding sites was significantly reduced in layers III and IV of the medial frontal, anterior, and posterior cingulate cortices, in layers II-IV of the retrosplenial cortex, in layers III-VI of the dorsal insular cortex, and in the reticular nucleus of the thalamus, compared to these numbers in a control group of rats that received physiologic saline. Further, chronic methamphetamine administration led to a significant increase in the number of these binding sites in layer I of the entorhinal cortex. These findings indicate the CCK peptides in the limbic lobe may be closely related to the development of the behavioral changes associated with methamphetamine sensitization. In addition, these results provide supporting evidence for the involvement of the limbic system in the pathophysiology of schizophrenia.

Animals↗

PubMed1980

Long-lasting depletions of striatal dopamine and loss of dopamine uptake sites following repeated administration of methamphetamine.

Repeated administration of high doses of methamphetamine produced long-term decreases in dopamine (DA) levels and in the number of DA uptake sites in the rat striatum. These two effects were dose-related and did not appear to be due to the continued presence of drug in striatal tissue. Long-lasting depletions induced by methamphetamine were selective for striatal DA neurons since norepinephrine (NE) levels in all of the rat brain regions examined were not changed on a long-term basis by methamphetamine treatments. Supersensitivity of DA receptors did not accompany the loss of striatal DA and its uptake sites.

Animals↗

PubMed1984

Hypothalamic alpha 2- and beta-adrenoceptor rhythms are correlated with circadian feeding: evidence from chronic methamphetamine treatment and withdrawal.

The circadian regulation of food intake in rats is correlated with a bimodal rhythm of beta-adrenoceptor binding in the lateral hypothalamus and a unimodal rhythm of alpha 2-adrenoceptor binding in the medial hypothalamus. Chronic methamphetamine treatment provides evidence for a functional correlation: beta-adrenoceptor binding in the lateral hypothalamus is reduced at dusk, together with reduction of food intake; alpha 2-adrenoceptor binding in the medial hypothalamus is increased at dawn, together with persistent food intake. Long-term changes in these two adrenergic systems are also correlated with homeostasis of food intake: 24-h mean beta-adrenoceptor binding is reduced and alpha 2-adrenoceptor binding is increased upon methamphetamine withdrawal, when rebound feeding occurs. Corticosterone, although normally coupled to adrenergic mechanisms that regulate feeding, is phase delayed after chronic methamphetamine treatment.

Animals↗

PubMed1989

Effects of high-dose methamphetamine administration on serotonin uptake sites in rat brain measured using [3H]cyanoimipramine autoradiography.

Repeated administration of high doses of methamphetamine (15 mg/kg given for 5 doses over 24 h) resulted in long-term decreases in the binding of [3H]cyanoimipramine ([3H]CN-IMI) to serotonin uptake sites measured using quantitative autoradiography. Seven days after termination of drug administration decreases were seen in 23 of 28 regions examined. This is consistent with previous studies indicating that methamphetamine and related amphetamines are neurotoxic to serotonin neurons. Significant decreases were still present in many brain areas on the same dosage schedule 30 days after drug administration. However, the number of areas affected was considerably less, consistent with some regrowth of serotonin neurons. At a lower dosage (7.5 mg/kg on the same schedule) no effects on [3H]CN-IMI binding were seen. The results of this study provide support for the serotonergic neurotoxicity of repeated methamphetamine administration in rats. They also show that the neurotoxicity is highly regional and dose dependent.

Animals↗

PubMed1991

Repeated injection of cocaine potentiates methamphetamine-induced toxicity to dopamine-containing neurons in rat striatum.

Rats were treated with daily injections of saline or cocaine (20 mg/kg i.p. x 15 days) and, beginning 24 h after the last injection, administered saline or methamphetamine (6.25-50 mg/kg s.c., BID x 4 days) and sacrificed two weeks later. Repeated daily administration of cocaine potentiated the long-lasting striatal dopamine depletions caused by methamphetamine. The results suggest that human use of cocaine may increase the likelihood of neurotoxicity resulting from ingestion of high doses of methamphetamine.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1977

Potentiating effect of lithium chloride on methamphetamine-induced stereotypy in mice.

Single administration of LiCl potentiated the methamphetamine-induced stereotypy in mice, without affecting the concentration of methamphetamine in brain. During MAO inhibition, the level of 3-methoxytyramine (3-MT), an O-methylated metabolite of dopamine, was reduced by LiCl, but the elevated 3-MT level observed after the administration of methamphetamine was not influenced by LiCl.

Animals↗

PubMed1981

Effect of L-histidine and chlorcyclizine on apomorphine-induced climbing behaviour and methamphetamine stereotypy in mice.

Pretreatment with L-histidine (850 and 1000 mh/kg, i.p.), a precursor of brain histamine, and chlorcyclizine (25 and 50 mg/kg, i.p.), a H1-receptor blocker, failed to modify apomorphine-induced climbing behaviour in mice. In contrast, pretreatment with L-histidine (850 and 1000 mg/kg) was found to antagonise methamphetamine stereotypy while pretreatment with chlorcyclizine (25 mg/kg) was found to potentiate methamphetamine-induced stereotypy in mice. The results suggest that drugs which influence central histaminergic mechanisms are effective only in modifying the behaviour induced by the indirectly acting DA agonist methamphetamine and fail to modify the behaviour induced by apomorphine, a directly acting DA agonist.

Animals↗

PubMed1987

Sulpiride injection into the dorsal striatum increases methamphetamine-induced gnawing in rats.

Sulpiride injected into the dorsal striatum enhanced both methamphetamine- and apomorphine-induced gnawing but blocked both when injected into the ventral striatum. The hyperlocomotion produced by methamphetamine was reduced by sulpiride injected into the dorsal striatum. The DA, DOPAC and HVA concentrations in the ventral striatum were increased 60 min after the injection of sulpiride into the dorsal striatum. Possible reasons for the enhancement of methamphetamine-induced gnawing by sulpiride injected into the dorsal striatum are discussed.

Animals↗

PubMed1991

D-alanine inhibits methamphetamine-induced hyperactivity in rats.

Bilateral intracerebroventricular injection of D-alanine (200-600 micrograms/rat) antagonized the ability of methamphetamine (1.0 mg/kg s.c.) to induce locomotor stimulation in the rat. In contrast, L-alanine (600 micrograms/rat) failed to affect the behavioral change induced by methamphetamine. The stereoselectivity parallels the potency of these amino acids as agonists for the strychnine-insensitive glycine binding site within the NMDA receptor complex. These results support the view that reduced excitatory amino acidergic neurotransmission may be involved in methamphetamine-induced hyperactivity.

Alanine↗