title: Dopaminergic modulation of cholinergic responses in rat medial prefrontal cortex: an electrophysiological study.
abstract: The neuromodulatory action of dopamine (DA) on acetylcholine (ACh)-evoked responses of prefrontal cortex (PFC) neurones were investigated electrophysiologically in rats anaesthetised with a combination of urethane and ketamine. Iontophoretic application of ACh-excited prefrontal cortex neurones. Concurrent application of DA (5-15 nA) resulted in complex changes in the ACh-evoked responses: (1) DA depressed spontaneous background discharges (designated as noise) proportionally more than the ACh-evoked discharges (designated as input signals), thus yielding an enhanced signal/noise ratio. This increase in signal/noise ratio by dopamine was reversed by iontophoretic application of the Da D2 antagonist sulpiride (20-50 nA). Nevertheless, iontophoretic application of D2 agonist quinpirole (5-35 nA) enhanced the ACh-evoked response, but was accompanied by some increase in spontaneous discharge, thus yielding no change in the signal/noise ratio. (2) DA also increased the signal/noise ratio by inducing a net increase of the ACh-evoked response but simultaneously suppressed the spontaneous activity of PFC neurones. This effect was more prominent following blockade of D1 receptors by SCH23390 (6 mg/kg, i.p.), suggesting that D1 receptors may normally inhibit D2 receptor function in the PFC. In addition, endogenous DA in the PFC did not play a significant part in modifying the ACh-evoked responses since the modulation of ACh-evoked response by DA or its D1 and D2 agonists was similar in both saline control and alpha-methyl-p-tyrosine-pretreated rats. (3) When ejected with larger iontophoretic current (16-35 nA), DA suppressed both the ACh-evoked and spontaneous discharge and this effect was mimicked by D1 agonist SKF38393 (5-15 nA). Taken together, these results suggest that complex dopaminergic modulation of the cholinergic responses of prefrontal cortex neurones are mediated by D1 and D2 receptors. This DA action may have a functional role in the cognitive-integrative processes occurring in the prefrontal cortex.
authors.affiliation: Dept. of Physiology, University of Western Ontario, London, Canada.
authors.forename: C R
authors.initials: CR
authors.lastname: Yang
authors.forename: G J
authors.initials: GJ
authors.lastname: Mogenson
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology; D004594:Electrophysiology / Q000379:methods; D004873:Ergolines / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D007478:Iontophoresis; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine
chemical_list: D001552:Benzazepines; D015259:Dopamine Agents; D004873:Ergolines; D008781:Methyltyrosines; D019257:Quinpirole; D019805:alpha-Methyltyrosine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D014446:Tyrosine 3-Monooxygenase; D000109:Acetylcholine; D004298:Dopamine