Brain-derived neurotrophic factor controls cannabinoid CB1 receptor function in the striatum.
1. Neostriatal neurones were recorded intracellularly from a rat corticostriatal slice preparation. Depolarizing postsynaptic potentials (DPSPs) were evoked by either cortical or intrastriatal stimulation. 2. Kynurenic acid (600 microM), an antagonist of excitatory amino acids, reduced the cortically-evoked DPSPs by 88% while the intrastriatally evoked potentials were reduced by 48%. Bicuculline (100 microM) produced only a slight inhibition of the cortically evoked DPSPs (12%), but clearly depressed intrastriatal potentials (52%). 3. The effects of (-)-baclofen, a gamma-aminobutyric acid (GABA)B receptor agonist, were studied on the cortically evoked DPSPs. In all the tested neurones (-)-baclofen, added to the superfusion medium, caused a concentration-dependent decrease of these potentials (half-maximal effect (EC50) = 800 nM). This effect was not affected by bicuculline. (-)-Baclofen did not change the membrane potential, the input resistance, current-evoked firing frequency, or postsynaptic responses to exogenously applied glutamate. 4. The effects of (-)-baclofen on the DPSPs were compared to those produced by application of GABA and muscimol. GABA and muscimol decreased the DPSPs and caused a membrane depolarization coupled with a decrease of the membrane resistance. Bicuculline (100 microM) blocked the GABA-induced changes of the membrane potential and of the resistance, but not the decrease of the synaptic potentials. All the effects produced by muscimol were blocked by bicuculline. 5. Following intrastriatal stimulation a residual kynurenate-insensitive potential persisted; this potential was blocked by bicuculline (100 microM). (-)-Baclofen produced a dose-dependent decrease of this potential (EC50 = 800 nM). The postsynaptic responses to exogenously applied GABA were unchanged by (-)-baclofen. 6. The amplitude of kynurenate and bicuculline-sensitive DPSPs were stable at a frequency of 0.1 Hz. At frequencies between 0.3 and 3 Hz both these potentials were attenuated with the second stimulus and after about five stimuli a steady state was reached. Membrane potential and input resistance were not affected by these frequencies of stimulation. 7. Application of the GABA uptake inhibitor nipecotic acid (100-300 microM) clearly reduced the amplitude of both kynurenate-and bicuculline-sensitive DPSPs evoked at low frequencies of stimulation (0.01-0.3 Hz), but had lower effects at higher stimulation rates (1-3 Hz). Application of nipecotic acid increased the duration of membrane responses to exogenously applied GABA.(ABSTRACT TRUNCATED AT 400 WORDS)