REGIONAL NEUROTRANSMITTER RESPONSES AFTER ACUTE AND CHRONIC ELECTROCONVULSIVE SHOCK

Regional neurotransmitter changes after acute and chronic electroconvulsive shock (ECS) were studied using the technique of repeated microdialysis. Microdialysis was carried out on alternate sides of the brains of anaesthetised rats before and during the first and the eighth ECS or sham (control) treatments. Extracellular fluid release of monoamines and their metabolites was measured in the frontal cortex, striatum and nucleus accumbens using HPLC with electrochemical detection. The first ECS produced selective regional responses, shown by increased concentrations of noradrenaline (NA) and dopamine (DA) in frontal cortex, by unchanged DA content in striatum, and by a small rise in NA and a fall in DA concentrations in nucleus accumbens. Concentrations of metabolites increased after ECS in all regions studied, and for homovanillic acid and dihydroxyphenylacetic acid, the temporal pattern of these changes did not resemble that of DA. Comparison of neurotransmitter responses as per cent of baseline release after the first and eighth ECS treatments showed they were identical. Basal release of monoamines and metabolites before the first ECS or sham treatment was similar in all regions studied. Prior to the eighth treatment, basal release of NA in the frontal cortex and DA in the striatum was elevated in the ECS-treated animals, while basal release of NA in the nucleus accumbens was reduced in both ECS-and sham-treated animals. These data suggest that acute and chronic ECS have different and region-specific effects on neurotransmitter release, although the overall pattern of these responses is not changed by chronic treatment. The catecholamine-releasing actions of ECS, and the changes in basal release of neurotransmitters seen after chronic treatment may contribute to its therapeutic effects. © 1990 Springer-Verlag

GBR12909 ANTAGONIZES THE ABILITY OF COCAINE TO ELEVATE EXTRACELLULAR LEVELS OF DOPAMINE

Rats were administered various IP doses of the high-affinity dopamine (DA) reuptake inhibitor 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-[phenylpropyl]piperazine (GBR12909). The caudate nuclei were removed 60 min after drug administration and stored at -70-degrees-C. Striatal membranes were prepared later. The results demonstrated that GBR12909 produced a dose-dependent decrease in the binding of [H-3]cocaine or [H-3]GBR12935 to the DA transporter (ED50 about 10 mg/kg). Saturation binding studies with [H-3]GBR12935 showed that this was due to both an increase in the K(d), due to residual drug, and to a decrease in the B(max). At a dose of 25 mg/kg IP, GBR12909 produced a 50% decrease in the B(max), and a 3.4-fold increase in the K(d). In the in vivo microdialysis studies, GBR12909 (25 mg/kg IP) produced a modest, long-lasting and stable elevation of extracellular DA. Administration of cocaine through the microdialysis probe to rats pretreated with either saline or GBR12909 (25 mg/kg IP) produced a dose-dependent increase in extracellular DA in both groups. GBR12909 inhibited cocaine-induced increases in extracellular DA by about 50% at all doses. These data collectively indicate that at a dose sufficient to decrease by 50% the B(max) of [H-3]GBR12935 binding sites, GBR12909 antagonizes the ability of cocaine to elevate extracellular DA by 50%. Further studies will be needed to evaluate a possible role for GBR12909 in the medical treatment of cocaine addiction