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This behavioural sensitization has been the subject of considerable interest due to its potential relevance to drug addiction. Repeated administration of d\u2010amphetamine also leads to an enhancement in the ability of electrical stimulation of the prefrontal cortex to induce burst firing in midbrain dopaminergic (DA) neurones. This hyper\u2010responsiveness probably reflects a potentiation of transmission at excitatory amino acid (EAA)ergic synapses on DA neurones. In addition, we have previously reported that selective activation of mineralocorticoid receptors (MRs) by corticosterone leads to a potentiation of EAA\u2010induced burst firing in midbrain DA neurones, an effect antagonized by glucocorticoid receptor (GR) activation. In this review article, we propose a model describing how drugs of abuse and stress alter EAA function at the level of DA cells in the ventral tegmental area (VTA), which can result in a long\u2010lasting impact on behaviour. D\u2010amphetamine produces a transitory increase in EAA\u2010mediated transmission at the level of DA cells in the VTA, which triggers a more long\u2010lasting change in EAAergic function resembling hippocampal long\u2010term potentiation. Dopaminergic burst events are likely to be a critical link between enhanced EAAergic activity in afferents synapsing on DA neurones and plasticity at these synapses, by increasing calcium transport into the cell, which is known to be an important factor in synaptic plasticity. Selective MR occupation by corticosterone in the VTA facilitates the development of this plasticity. However, we hypothesize that during stress, GR\u2010occupation also activates EAAergic afferents to DA neurones in a manner similar to that following psychostimulants. Under these circumstances, GR\u2010occupation acts via circuitry external to the VTA, which may include the hippocampus. Thus, potentiation of EAAergic synapses on DA neurones in the VTA may represent a final common pathway by which two divserse means (psychostimulants and stress) achieve the same end (sensitization). Alterations in EAA\u2010mediated transmission at the level of DA cells not only plays a critical role in the induction of behavioural sensitization, but probably continues to produce abnormal DA cell responses in the drug\u2010free situation.<\/jats:p>","DOI":"10.1080\/13556219872191","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:11:58Z","timestamp":1027699918000},"page":"109-135","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Alterations in excitatory amino acid\u2010mediated regulation of midbrain dopaminergic neurones induced by chronic psychostimulant administration and stress: relevance to behavioural sensitization and drug addiction"],"prefix":"10.1111","volume":"3","author":[{"given":"DAVID","family":"CLARK","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"PAUL 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