Local injection of a glutamate uptake inhibitor into the ventral tegmental area produces sensitization to the behavioural effects of d-amphetamine
| Autor: | Paul G. Overton, David Clark, J. Aked, Véronique Coizet |
|---|---|
| Přispěvatelé: | Department of Psychology [Sheffield], University of Sheffield [Sheffield], Department of Psychology, Swansea University, Savasta, Marc |
| Rok vydání: | 2005 |
| Předmět: |
Male
Dextroamphetamine Pyrrolidines MESH: Rats Microinjections MESH: Piperazines Glutamic Acid Pharmacology Motor Activity MESH: Microinjections Piperazines MESH: Dextroamphetamine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine MESH: Dicarboxylic Acids medicine Animals MESH: Animals Dicarboxylic Acids Amphetamine Neurotransmitter Sensitization 030304 developmental biology 0303 health sciences MESH: Pyrrolidines Chemistry General Neuroscience Ventral Tegmental Area Glutamate receptor Rats Inbred Strains Glutamic acid MESH: Excitatory Amino Acid Antagonists MESH: Glutamic Acid MESH: Rats Inbred Strains MESH: Male MESH: Motor Activity Rats Ventral tegmental area medicine.anatomical_structure Anesthesia MESH: Ventral Tegmental Area NMDA receptor Excitatory Amino Acid Antagonists 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neuroscience Neuroscience, Elsevier-International Brain Research Organization, 2005, 134 (2), pp.361-7. ⟨10.1016/j.neuroscience.2005.04.044⟩ |
| ISSN: | 0306-4522 1873-7544 |
| DOI: | 10.1016/j.neuroscience.2005.04.044⟩ |
| Popis: | International audience; Circumstantial evidence suggests that sensitization to the behavioral effects of d-amphetamine is mediated by increased glutamate levels in the ventral tegmental area. To test this directly, the present study examined whether increasing glutamate levels in the ventral tegmental area with a glutamate uptake inhibitor is sufficient, in the absence of d-amphetamine administration, to elicit sensitization to a subsequent d-amphetamine challenge. Rats were treated bilaterally once a day for 2 days with either intra-ventral tegmental area L-trans-pyrollidine-2,4-dicarboxylic acid (50 nmol), saline, L-trans-pyrollidine-2,4-dicarboxylic acid coadministered with the competitive N-methyl-d-aspartate antagonist (+/-)-3-(2-carboxy-piperazin-4-yl)-propyl-1-phosphonic acid; CPP, 0.5 nmol), or CPP alone (0.5 nmol; all 1.0 microl/side). Following a 2 day withdrawal period, all rats were administered systemic d-amphetamine (1 mg/kg, i.p.). Repeated intra-ventral tegmental area injection of L-trans-pyrollidine-2,4-dicarboxylic acid sensitized animals to the behavioral effects of a systemic d-amphetamine challenge, an action which was blocked by co-administration of CPP. The results directly implicate ventral tegmental area glutamate in the process of sensitization to d-amphetamine. Furthermore, they demonstrate that inhibition of glutamate uptake produces the neuroadaptations necessary to induce sensitization, adding support to the contention that d-amphetamine sensitizes by modulating glutamate uptake. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect