D-amphetamine potentiates muscimol-induced disinhibition of A10 dopaminergic neurons in the rat

Evidence suggests that sensitisation to the behavioural effects of d-amphet amine involves a late-onset (>3 hrs), long-term potentiation (LTP)like chan ge at medial prefrontal cortex (mPFC)-regulated synapses on A10 dopaminergi c (DA) neurons. Since muscimol-induced excitation of A10 DA neurons is depe ndent 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-naive 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. Mus cimol produced significantly less inhibition of A10 DA neurons from animals administered d-amphetamine (rather than saline), but only when d-amphetami ne had been chronically administered beforehand (i.e. in the challenge cond ition). Hence, although the studies fail to provide evidence that acute d-a mphetamine administration produces the conditions necessary for LTP, chroni c d-amphetamine administration appears to potentiate the impact on A10 DA n eurons of mPFC-regulated excitatory activity, thus strengthening the link b etween this potentiation and the sensitisation process.