A comparison of amphetamine- and methamphetamine-induced locomotor activity in rats: evidence for qualitative differences in behavior

Hall, Darien A.; Stanis, Jessica J.; Avila, Hector Marquez; Gulley, Joshua M.

doi:10.1007/s00213-007-0923-8

Cited by 84 publications

(71 citation statements)

References 24 publications

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“…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).…”

Section: The Dopamine Transporter (Dat)mentioning

confidence: 86%

“…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).…”

Section: The Dopamine Transporter (Dat)mentioning

confidence: 99%

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

Goodwin

Larson

Swant

et al. 2009

Journal of Biological Chemistry

181

148

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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. 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

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Section: The Dopamine Transporter (Dat)mentioning

confidence: 86%

Section: The Dopamine Transporter (Dat)mentioning

confidence: 99%

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

Goodwin

Larson

Swant

et al. 2009

Journal of Biological Chemistry

181

148

View full text Add to dashboard Cite

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“…Conditioned locomotor activity is a measure of contextual salience attribution and depends on mPFC function (Stewart et al, 1984;Cervo and Samanin, 1996;Di Ciano et al, 1998;Franklin and Druhan, 2000;Hall et al, 2008;Berridge, 1993, 2008). Whereas the amphetamine regimen used in this experiment produced exaggerated salience attribution when administered in adolescence, it failed to induce salience attribution when administered in adulthood.…”

Section: Dcc-mediated Effects Of Amphetamine On the Sculpting Of Mpfcmentioning

confidence: 99%

Amphetamine in Adolescence Disrupts the Development of Medial Prefrontal Cortex Dopamine Connectivity in a dcc-Dependent Manner

Reynolds

Makowski

Yogendran

et al. 2014

Neuropsychopharmacol

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Initiation of drug use during adolescence is a strong predictor of both the incidence and severity of addiction throughout the lifetime. Intriguingly, adolescence is a period of dynamic refinement in the organization of neuronal connectivity, in particular medial prefrontal cortex (mPFC) dopamine circuitry. The guidance cue receptor, DCC (deleted in colorectal cancer), is highly expressed by dopamine neurons and orchestrates their innervation to the mPFC during adolescence. Furthermore, we have shown that amphetamine in adolescence regulates DCC expression in dopamine neurons. Drugs in adolescence may therefore induce their enduring behavioral effects via DCC-mediated disruption in mPFC dopamine development. In this study, we investigated the impact of repeated exposure to amphetamine during adolescence on both the development of mPFC dopamine connectivity and on salience attribution to drug context in adulthood. We compare these effects to those induced by adult exposure to an identical amphetamine regimen. Finally, we determine whether DCC signaling within dopamine neurons is necessary for these events. Exposure to amphetamine in adolescence, but not in adulthood, leads to an increase in the span of dopamine innervation to the mPFC, but a reduction of presynaptic sites present on these axons. Amphetamine treatment in adolescence, but not in adulthood, also produces an increase in salience attribution to a previously drug-paired context in adulthood. Remarkably, DCC signaling within dopamine neurons is required for both of these effects. Drugs of abuse in adolescence may therefore induce their detrimental behavioral consequences by disrupting mesocortical dopamine development through alterations in the DCC signaling cascade.

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“…The procedure for drug administration and testing was identical to that described above. The low dose of METH was chosen to induce forward locomotion and no stereotypy [34] .…”

Section: Test Of Cross-sensitization To Methmentioning

confidence: 99%

Weekly γ-Hydroxybutyrate Exposure Sensitizes Locomotor Hyperactivity to Low-Dose 3,4-Methylenedioxymethamphetamine in Rats

Nieuwenhuijzen¹,

Li²,

Hunt

et al. 2009

Neuropsychobiology

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Users of the popular party drug 3,4-methylenedioxymethamphetamine (MDMA) sometimes report combining MDMA with γ-hydroxybutyrate (GHB) to enhance the pleasurable effects of both drugs. However, very few studies have examined the influences of this drug combination. The present study investigated the development of locomotor sensitization in laboratory rats given 7 once-weekly exposures to either MDMA, GHB or their combination (MDMA/GHB). The drugs were administered at a high ambient temperature (28°C) to mimic nightclub conditions. MDMA (5 mg/kg), given once weekly, produced a progressively greater locomotor and hyperthermic response over time. In contrast, GHB (500 mg/kg) administered weekly produced consistent low levels of locomotor activity and few changes in body temperature. Rats receiving the mixture of MDMA (5 mg/kg) and GHB (500 mg/kg) showed asymptotic levels of sensitized locomotor activity similar to those seen in rats given MDMA alone, but the development of locomotor sensitization was delayed by coadministered GHB. GHB also delayed the development of MDMA-induced hyperthermia. After a washout period of 5 weeks, rats pre-exposed to MDMA, GHB and MDMA/GHB showed no hyperactivity when tested drug-free in the context in which they had previously received drugs, but displayed a sensitized locomotor response to a low challenge dose of MDMA (2.5 mg/kg). The response to a low dose of methamphetamine (0.5 mg/kg) did not differ among groups. Neurochemical analysis using high-performance liquid chromatography revealed few lasting changes in serotonin, dopamine or their metabolites in the striatum or prefrontal cortex of MDMA- or GHB-pre-exposed rats. These results indicate that GHB modulates the locomotor and hyperthermic response to acute MDMA and that pre-exposure to GHB can sensitize the locomotor response to low doses of MDMA.

show abstract

A comparison of amphetamine- and methamphetamine-induced locomotor activity in rats: evidence for qualitative differences in behavior

Cited by 84 publications

References 24 publications

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

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

Amphetamine in Adolescence Disrupts the Development of Medial Prefrontal Cortex Dopamine Connectivity in a dcc-Dependent Manner

Weekly γ-Hydroxybutyrate Exposure Sensitizes Locomotor Hyperactivity to Low-Dose 3,4-Methylenedioxymethamphetamine in Rats

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