D-Amphetamine potentiates muscimol-induced disinhibition of A10 dopaminergic neurons in the rat.
Evidence suggests that sensitisation to the behavioural effects of d-amphetamine involves a late-onset (>3 hrs), long-term potentiation (LTP)-like change at medial prefrontal cortex (mPFC)-regulated synapses on A10 dopaminergic (DA) neurons. Since muscimol-induced excitation of A10 DA neurons is dependent on mPFC-regulated afferents, this assay was used to assess whether d-amphetamine enhances the driving of A10 DA neurons by the mPFC, as would be predicted if it resulted in the conditions necessary for LTP. Animals were administered d-amphetamine or saline, 3-4.5 hrs prior to recording. In the acute condition, animals were drug-naïve prior to d-amphetamine, whilst in the challenge condition, animals had previously received d-amphetamine (or saline) each day for 6 days. Recording took place on withdrawal day 2. Muscimol produced significantly less inhibition of A10 DA neurons from animals administered d-amphetamine (rather than saline), but only when d-amphetamine had been chronically administered beforehand (i.e. in the challenge condition). Hence, although the studies fail to provide evidence that acute d-amphetamine administration produces the conditions necessary for LTP, chronic d-amphetamine administration appears to potentiate the impact on A10 DA neurons of mPFC-regulated excitatory activity, thus strengthening the link between this potentiation and the sensitisation process.


BACKGROUND
Ventral tegmental area, excitatory amino acids, medial prefrontal cortex, non-DA neurons, synaptic plasticity, behavioural sensitisation.
Overton
P G
PG
Department of Psychology, University of Wales, Swansea, United Kingdom. p.g.overton@herts.ac.uk
Lokwan
S J
SJ
Berry
M S
MS
Clark
D
D
D000704:Analysis of Variance; D000818:Animals; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D009118:Muscimol / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
D009118:Muscimol; D003913:Dextroamphetamine