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Dopamine receptor binding in the caudate-putamen was studied following bilateral lesions of the thalamostriatal pathway. Receptor binding was assayed using [3H]spiperone and defined with both (+)-butaclamol and S(-)-sulpiride. Radiofrequency lesions resulted in an increase in the Bmax of [3H]spiperone binding defined with both (+)-butaclamol and S(-)-sulpiride between 7 and 14 days following surgery. At longer survival times a fluctuating response was seen in which a decrease in receptor binding was observed at 28 days following lesion and a further rise again at 70 days. At no time point was significant change in Kd recorded. Further experiments were carried out to control for the possible effects of damage to fibres of passage and for inadvertent damage to habenula, as well as to define the receptor subtype involved. Ibotenic acid lesions resulted in similar effects to those reported with the radiofrequency method. Thus, 7 days following lesion, Bmax for (+)-butaclamol-defined [3H]spiperone binding increased by approximately 14-20% over that recorded in sham-lesioned animals. Using S(-)-sulpiride to define binding, Bmax was found to increase 13-17% in the same membrane preparations. Similar results were obtained in experiments at 14 days following ibotenic acid induced lesions. Again, no change in Kd was recorded. When radiofrequency lesions were made, which were largely restricted to habenula and associated fibres of passage, only small [(+)-butaclamol defined] or insignificant [S(-)-sulpiride defined] changes in Bmax were recorded. Combined radiofrequency lesions of habenula and ibotenic acid lesions of the thalamus resulted in a larger increase in Bmax for (+)-butaclamol defined binding than with S(-)-sulpiride defined binding. Our interpretation of these findings, in the light of the histology of the lesions, is that the predominant effect of removing thalamic input to the caudate-putamen is an increase in the number of D2 receptors, but without any change of affinity. A small component of the change in Bmax defined with (+)-butaclamol found with radiofrequency lesions may be due to a response at non-dopamine sites (possibly a 5-hydroxytryptamine receptor subtype) following damage to other caudate-putamen afferents which pass near the habenula or fasciculus retroflexus. Following unilateral ibotenic acid lesions of the thalamus, the number of high affinity uptake sites for dopamine was increased at long survival times.(ABSTRACT TRUNCATED AT 400 WORDS)

Dopamine (DA) utilisation has been determined in the medial bank of the prefrontal cortex (FCx) and the agranular insular cortex (AgCx) of the rat in response to a unilateral reduction of gamma-aminobutyric acid (GABA)-mediated inhibition in the thalamic mediodorsal nucleus (MD). The ratios of 3,4-dihydroxyphenylacetic acid (DOPAC): DA and 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid, HVA): DA were used as indices of DA utilisation. A bilateral increase in both ratios was found in FCx and AgCx following unilateral infusion of GABA antagonists (1 mM) into MDc. When this concentration was infused into one MDL no change was detected in DA utilisation of FCx, although a bilateral increase was observed in AgCx. However, a correspondence with the known anatomical connections was attained following infusion of lower concentrations (0.5 mM) into MDL in that a significant bilateral elevation of DA utilisation was shown in FCx. The changes induced in these ratios by the above treatments were, in general, due to increases in the concentration of metabolite and slight decreases in that of DA. However, unilateral lesions to the presumed GABA-containing neurones of the rostrodorsal thalamic reticular nucleus (TRNd), which topographically innervate MDL, produced increases in both metabolite and DA concentrations in FCx of both hemispheres, whilst those in AgCx were unaffected. Despite the slightly different results obtained using these two experimental approaches, it is argued that a reduction of tonic GABA-mediated inhibition in MD may tend to activate the DA system in cortical target regions.

Dopamine (DA) utilisation has been assessed in medial and lateral segments of the caudate-putamen complex (CPM and CPL, respectively) in response to unilateral manipulations aimed at the thalamic mediodorsal nucleus, lateral division (MDL). The ratios of 3,4-dihydroxyphenylacetic acid (DOPAC):DA and 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid, HVA):DA are used as indices of DA utilisation and, in the case of HVA:DA, may also reflect DA release. Neither electrical stimulation nor ibotenate (IBO) treatment followed by long recovery periods (2 days or 1 week) had any significant effect on DA utilisation in CPM or CPL. Cell-specific activation of neurones produced by short-term (1 h recovery) infusions of IBO aimed unilaterally at MDL (right side) resulted in bilateral increases of DA utilisation in both CP sectors. These changes tended to be slightly more marked in the hemisphere ipsilateral to the side of IBO infusion. Unilateral infusions of IBO were then aimed at MDL of either (1) the left or right hemisphere of animals which had already received a 1-week-old unilateral (right side) prefrontal cortex (FCx) lesion or (2) the right hemisphere of animals which had previously received a 1 week-old bilateral FCx lesion. The pattern of changes, when expressed relative to the 'sham-operated' animals which received the FCx lesion alone, were similar to those described above following intra-MDL infusions of IBO into animals with an intact cortex. The FCx lesions themselves were shown to have no significant effect on DA utilisation in any CP sector. In view of the known neuroanatomical connections, it is likely that the effects observed in CP are not due to activation of MDL neurones themselves but are more likely the result of activation of neurones in the intralaminar nuclei which border MDL. Nevertheless, these findings support the concept that activation of thalamic nuclei will enhance DA function in a variety of forebrain areas in the rat.

Certain sulphur-containing amino acids are putative excitatory transmitters in the mammalian central nervous system. The quantification and a partial regional analysis of these compounds in the rat brain is presented. Our findings show that (S)-(+)-homocysteate, determined for the first time, is the most concentrated of those sulphonic and sulphinic amino acids assayed here.