Supranormal Stimulation of D1Dopamine Receptors in the Rodent Prefrontal Cortex Impairs Spatial Working Memory Performance
10.1523/jneurosci.17-21-08528.1997
Crossref journal-article
Society for Neuroscience
The Journal of Neuroscience (393)
Abstract

Although previous research has emphasized the beneficial effects of dopamine (DA) on functions of the prefrontal cortex (PFC), recent studies of animals exposed to mild stress indicate that excessive DA receptor stimulation may be detrimental to the spatial working memory functions of the PFC (Arnsten and Goldman-Rakic, 1990; Murphy et al., 1994, 1996a,b, 1997). In particular, these studies have suggested that supranormal stimulation of D1receptors may contribute to the detrimental actions of DA in the PFC (Murphy et al., 1994, 1996a). The current study directly tested this hypothesis by examining the effects of infusing a full D1receptor agonist, SKF 81297, into the PFC of rats performing a spatial working memory task, delayed alternation. SKF 81297 produced a dose-related impairment in delayed-alternation performance. The impairment was reversed by pretreatment with a D1receptor antagonist, SCH 23390, consistent with drug actions at D1receptors. SCH 23390 by itself had no effect on performance, although slightly higher doses impaired performance (Murphy et al., 1994, 1996a). There was a significant relationship between infusion location and drug efficacy; animals with cannulae anterior to the PFC were not impaired by SKF 81297 infusions. Taken together, these results demonstrate that supranormal D1receptor stimulation in the PFC is sufficient to impair PFC working memory function. These cognitive data are consistent with recent electrophysiological studies of D1receptor mechanisms affecting the PFC (Williams and Goldman-Rakic, 1995; Yang and Seamans, 1996). Increased D1receptor stimulation during stress may serve to take the PFC “off-line” to allow posterior cortical and subcortical structures to regulate behavior, but may contribute to the vulnerability of the PFC in many neuropsychiatric disorders.

Bibliography

Zahrt, J., Taylor, J. R., Mathew, R. G., & Arnsten, A. F. T. (1997). Supranormal Stimulation of D1Dopamine Receptors in the Rodent Prefrontal Cortex Impairs Spatial Working Memory Performance. The Journal of Neuroscience, 17(21), 8528–8535.

Authors 4
  1. Justin Zahrt (first)
  2. Jane R. Taylor (additional)
  3. Rex G. Mathew (additional)
  4. Amy F. T. Arnsten (additional)
References 49 Referenced 638
  1. 10.1016/0922-4106(90)90194-3
  2. 10.1177/026988119701100208
  3. {'key': '2023041302370023000_17.21.8528.3', 'first-page': '1464', 'article-title': 'Reversal of stress-induced delayed response deficits in rhesus monkeys by clonidine and naloxone.', 'volume': '12', 'author': 'Arnsten', 'year': '1986', 'journal-title': 'Soc Neurosci Abstr'} / Soc Neurosci Abstr / Reversal of stress-induced delayed response deficits in rhesus monkeys by clonidine and naloxone. by Arnsten (1986)
  4. {'key': '2023041302370023000_17.21.8528.4', 'first-page': '164', 'article-title': 'Stress impairs prefrontal cortex cognitive function in monkeys: role of dopamine.', 'volume': '16', 'author': 'Arnsten', 'year': '1990', 'journal-title': 'Soc Neurosci Abstr'} / Soc Neurosci Abstr / Stress impairs prefrontal cortex cognitive function in monkeys: role of dopamine. by Arnsten (1990)
  5. 10.1007/BF02245056
  6. 10.1192/bjp.162.1.72
  7. {'key': '2023041302370023000_17.21.8528.7', 'first-page': '262', 'article-title': 'Methylphenidate and neuroleptic effects on oral word production in schizophrenia.', 'volume': '5', 'author': 'Bilder', 'year': '1992', 'journal-title': 'Neuropsychiatr Neuropsychol Behav Neurol'} / Neuropsychiatr Neuropsychol Behav Neurol / Methylphenidate and neuroleptic effects on oral word production in schizophrenia. by Bilder (1992)
  8. Breier A Wolkowitz OM Pickar D (1991) Stress and schizophrenia. Advances in neuropsychiatry and psychopharmacology. in Schizophrenia research, Vol 1, eds Tamminga CA Schult SC (Raven, New York).
  9. 10.1126/science.112679
  10. 10.1016/0166-4328(90)90091-R
  11. {'key': '2023041302370023000_17.21.8528.11', 'first-page': '1', 'article-title': 'Dose-dependent effects of the dopamine D1 receptor agonists A77636 or SKF81297 on spatial working memory in aged monkeys.', 'volume': '282', 'author': 'Cai', 'year': '1997', 'journal-title': 'J Pharmacol Exp Ther'} / J Pharmacol Exp Ther / Dose-dependent effects of the dopamine D1 receptor agonists A77636 or SKF81297 on spatial working memory in aged monkeys. by Cai (1997)
  12. 10.1016/0014-4886(80)90150-8
  13. 10.1523/JNEUROSCI.11-07-01907.1991
  14. 10.1176/ajp.148.11.1474
  15. 10.1016/S0079-6123(08)62691-6
  16. Deutch AY Zahm DS Bourdelais AJ (1993) The nucleus accumbens core and shell: delineation of cortico-striatal circuits and their functional attributes. in Limbic motor circuits and neuropsychology, eds Kalivas PW Barnes CD (CRC, Boca Raton, FL), pp 45–88.
  17. Dohrenwend BP Shrout PE Link BG Skodol AE Stueve A (1995) Life events and other possible psychosocial risk factors for episodes of schizophrenia and major depression: a case-control study. in Progress in psychiatry, Vol 46, Does stress cause psychiatric illness? ed Mazure CM (American Psychiatric, Washington, DC), pp 43–65.
  18. 10.1523/JNEUROSCI.16-21-07055.1996
  19. {'key': '2023041302370023000_17.21.8528.19', 'first-page': '237', 'article-title': 'Reduction in dendritic spine number on cortical pyramidal neurons in schizophrenia.', 'volume': '21', 'author': 'Garey', 'year': '1995', 'journal-title': 'Soc Neurosci Abstr'} / Soc Neurosci Abstr / Reduction in dendritic spine number on cortical pyramidal neurons in schizophrenia. by Garey (1995)
  20. {'key': '2023041302370023000_17.21.8528.20', 'first-page': '239', 'article-title': 'Assessment of spine density on layer III pyramidal cells in the prefrontal cortex of schizophrenic subjects.', 'volume': '21', 'author': 'Glantz', 'year': '1995', 'journal-title': 'Soc Neurosci Abstr'} / Soc Neurosci Abstr / Assessment of spine density on layer III pyramidal cells in the prefrontal cortex of schizophrenic subjects. by Glantz (1995)
  21. Goldman-Rakic PS (1987) Circuitry of the primate prefrontal cortex and the regulation of behavior by representational memory. in Handbook of physiology, The nervous system, Higher functions of the brain, Sec 1, Vol V, Pt 1, ed Plum F (American Physiological Society, Bethesda, MD), pp 373–417. (10.1002/cphy.cp010509)
  22. 10.1523/JNEUROSCI.16-15-04787.1996
  23. 10.1007/BF01245228
  24. 10.1037/0735-7044.103.5.956
  25. Kolb B (1990) Prefrontal cortex. in The cerebral cortex of the rat, eds Kolb B Tees RC (MIT, Cambridge, MA), pp 437–458.
  26. 10.3758/BF03326684 / Physiol Psychol / Selective ablations within the prefrontal cortex of the rat and performance of delayed alternation. by Larsen (1978)
  27. Mishkin M (1964) Perseveration of central sets after frontal lesions in monkeys. in The frontal granular cortex and behavior, eds Warren JM Akert K (McGraw-Hill, New York), pp 219–241.
  28. {'key': '2023041302370023000_17.21.8528.28', 'first-page': '1018', 'article-title': 'The effects of FG7142 on prefrontal cortical dopamine and spatial working memory in rat and monkey.', 'volume': '20', 'author': 'Murphy', 'year': '1994', 'journal-title': 'Soc Neurosci Abstr'} / Soc Neurosci Abstr / The effects of FG7142 on prefrontal cortical dopamine and spatial working memory in rat and monkey. by Murphy (1994)
  29. 10.1073/pnas.93.3.1325
  30. 10.1523/JNEUROSCI.16-23-07768.1996
  31. 10.1016/S0893-133X(97)00019-5
  32. 10.1016/S0079-6123(08)62679-5 / Prog Brain Res / Prefrontal control of the autonomic nervous system: anatomical and physiological observations. by Neafsey (1990)
  33. 10.1016/0306-4522(91)90150-M
  34. 10.1126/science.1825731
  35. {'key': '2023041302370023000_17.21.8528.35', 'first-page': '417', 'article-title': 'Modulatory role of D1-dopamine receptors in mnemonic coding of monkey prefrontal cortical neurons.', 'volume': '22', 'author': 'Sawaguchi', 'year': '1996', 'journal-title': 'Soc Neurosci Abstr'} / Soc Neurosci Abstr / Modulatory role of D1-dopamine receptors in mnemonic coding of monkey prefrontal cortical neurons. by Sawaguchi (1996)
  36. 10.1016/0168-0102(88)90030-2
  37. {'key': '2023041302370023000_17.21.8528.37', 'first-page': '664', 'article-title': 'Strukturwandel neokortikaler Pyramidenneurone des Menschen wahrend des 5. bis 9. Dezenniums.', 'volume': '33', 'author': 'Schierhorn', 'year': '1981', 'journal-title': 'Psychiatr Neurol Med Psychol'} / Psychiatr Neurol Med Psychol / Strukturwandel neokortikaler Pyramidenneurone des Menschen wahrend des 5. bis 9. Dezenniums. by Schierhorn (1981)
  38. {'key': '2023041302370023000_17.21.8528.38', 'first-page': '1942', 'article-title': 'Selective impairment on a delayed radial arm task following local administration of a selective D1, but not a D2, antagonist into the prefrontal cortex.', 'volume': '21', 'author': 'Seamans', 'year': '1995', 'journal-title': 'Soc Neurosci Abstr'} / Soc Neurosci Abstr / Selective impairment on a delayed radial arm task following local administration of a selective D1, but not a D2, antagonist into the prefrontal cortex. by Seamans (1995)
  39. 10.1523/JNEUROSCI.17-15-05936.1997
  40. 10.1016/S0022-3565(25)24159-3 / J Pharmacol Exp Ther / Pharmacological characterization of the receptor mediating electrophysiological responses to dopamine in the rat medial prefrontal cortex: a microiontophoretic study. by Sesack (1989)
  41. {'key': '2023041302370023000_17.21.8528.41', 'first-page': '81', 'article-title': 'Dopaminergic A10 neurons and the frontal system.', 'volume': '77', 'author': 'Simon', 'year': '1981', 'journal-title': 'J Physiol (Paris)'} / J Physiol (Paris) / Dopaminergic A10 neurons and the frontal system. by Simon (1981)
  42. 10.1038/263242a0
  43. 10.1016/0361-9230(86)90027-4
  44. 10.1016/0014-4886(80)90151-X
  45. 10.1016/0166-4328(85)90167-6
  46. 10.1523/JNEUROSCI.16-01-00373.1996
  47. 10.1038/376572a0
  48. 10.1523/JNEUROSCI.16-05-01922.1996
  49. 10.1523/JNEUROSCI.09-03-00898.1989
Dates
Type When
Created 7 years, 4 months ago (April 2, 2018, 8:21 p.m.)
Deposited 1 month, 4 weeks ago (July 3, 2025, 6:35 a.m.)
Indexed 4 days, 8 hours ago (Aug. 27, 2025, 12:02 p.m.)
Issued 27 years, 9 months ago (Nov. 1, 1997)
Published 27 years, 9 months ago (Nov. 1, 1997)
Published Online 27 years, 9 months ago (Nov. 1, 1997)
Published Print 27 years, 9 months ago (Nov. 1, 1997)
Funders 0

None

@article{Zahrt_1997, title={Supranormal Stimulation of D1Dopamine Receptors in the Rodent Prefrontal Cortex Impairs Spatial Working Memory Performance}, volume={17}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.17-21-08528.1997}, DOI={10.1523/jneurosci.17-21-08528.1997}, number={21}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Zahrt, Justin and Taylor, Jane R. and Mathew, Rex G. and Arnsten, Amy F. T.}, year={1997}, month=nov, pages={8528–8535} }