The effect of posttraining intracerebral injections of the indirect dopamine (DA) agonist d-amphetamine, the direct D2 agonist LY 171555, and the direct D1 agonist SKF-38393 on the acquisition of two 8-arm radial maze tasks were examined. On a win-stay task, a light cue signaled the location of food in 4 randomly selected maze arms on each trial, and animals were required to visit each of the lit arms twice within a trial. Posttraining intracaudate injection of d-amphetamine (10.0 and 15.0 micrograms), LY 171555 (2.0 micrograms), and SKF-38393 (5.0 micrograms) all improved win-stay acquisition in relation to saline-injected controls. In contrast, posttraining intrahippocampal injection of DA agonists had no effect on win-stay acquisition. On a win-shift task, rats were allowed to obtain food from 4 randomly selected maze arms, followed by a delay period in which they were removed from the maze. They were returned to the maze for a retention test in which only those arms that had not been visited before the delay contained food. Posttraining intrahippocampal (but not intracaudate) injection of d-amphetamine (5.0 micrograms), LY 171555 (2.0 micrograms), and SKF-38393 (5.0 micrograms) all improved win-shift retention in relation to saline-injected controls. The results demonstrate a double dissociation of hippocampus and caudate nucleus memory functions and show that posttraining injection of both D1 and D2 agonists modulate the memory processes subserved by both hippocampus and caudate nucleus.

Dissociation of hippocampus and caudate nucleus memory systems by posttraining intracerebral injection of dopamine agonists

The late maintenance of hippocampal LTP: Requirements, phases, ‘synaptic tagging’, ‘late-associativity’ and implications

In search of cellular mechanisms of memory

Polymyxin B, an inhibitor of protein kinase C, prevents the maintenance of synaptic long-term potentiation in hippocampal CA1 neurons

Fucokinase (EC 2.7.1.52) activity was estimated in supernatants of homogenate from day-old chick forebrain. Enzyme kinetic studies gave a Km of 4.5 X 10(-6) M and Vmax of 3.72 nmol fucose converted into fucose-1-phosphate/mg prot/h. The pH optimum was 7.5. The enzyme is thus considerably more active than was reported for other species and tissues. There were no differences in enzyme activity between the four forebrain regions studied. One hour after chicks were trained on a one-trial passive avoidance learning paradigm, enzyme activity in the right forebrain base increased 14% over control values (p less than 0.02). The 11.3% increase in activity in the left forebrain base and 10.3% increase in the left roof were not statistically significant. The relationship of this change to the increased fucose incorporation into glycoproteins known to occur over a similar time period and the significance of the lateralization of the increase are discussed.

Passive avoidance training increases fucokinase activity in right forebrain base of day-old chicks.

In hippocampus slices both dopamine and apomorphine lead to an increased incorporation of (3H)-fucose into total proteins, whereas the incorporation of (14C)-leucine was unchanged or decreased, respectively. Noradrenaline did not alter the incorporation of both precursors, whereas haloperidol partially reduced the dopamine induced increased in incorporation of fucose. Thus, an induction process of the observed macromolecular changes involving dopaminoceptive structures of hippocampus can be assumed.

Dopamine and macromolecule synthesis in rat hippocampus

The effect of rhythmic slow wave activity (theta rhythm) on the incorporation of 3H-leucine and 3H-fucose into the total proteins of different hippocampus areas was studied. The theta rhythm was elicited by electrical stimulation of medial septum nuclei. An increase in 3H-leucine incorporation into the total proteins of CA 3 and CA 1 sectors of the hippocampus was observed, whereas the stimulation had no influence on precursor incorporation into the complex CA 4/area dentata. In contrast to these findings 3H-fucose incorporation into hippocampal proteins was not influenced by electrical stimulation of the medial septum. These findings are discussed in comparison to the results obtained in a learning experiment, which revealed an increased incorporation of both leucine and focuse into hippocampal proteins.

Hippocampal activation and incorporation of macromolecule precursors

Apomorphine intrahippocampally injected at a dose of 5 μg led to a significant increase in incorporation of ( 3 H)-fucose into total proteins of this brain area, whereas 40 μg led to a significant decrease in comparison to controls, providing further evidence for the existence of dopaminoceptive structures in the hippocampus of rats and their significance for glycoprotein metabolism.

Apomorphine and glycoprotein synthesis in rat hippocampus

Dopamine increases the incorporation of L-fucose and of D-mannose to a similar significant degree, whereas the incorporation of D-galactose as well as of N-acetyl-D-glucosamin into the total proteins of hippocampal slices was only slightly enhanced. The incorporation of N-acetyl-neuraminic acid was not influenced by dopamine. The results suggest that the effect of dopamine on glycoprotein formation seems mainly to depend on the kind of nucleotides necessary for activation of sugars and not on the sugar's final position in the glycan chain.

The influence of dopamine on the incorporation of different sugars into total proteins of hippocampal slices

In 60 day old (adult) male Wistar rats dopamine caused a dose-dependent increase of L-fucose incorporation into total proteins of both hippocampus and corpus striatum slices up to +47.8±6.0% (n=6) and +53.2±8.5% (n=20), respectively, when compared to corresponding controls. Under these conditions the dopamine concentration leading to a maximum stimulation of fucose incorporation was 5×10−4 M in hippocampus and 1×10−3 M in corpus striatum. In the latter tissue the range of dopamine concentrations causing a significant elevation in incorporation rates was larger than in hippocampal tissue. In the corpus striatum of 9 day old rats dopamine was ineffective, but by 30 days the transmitter stimulated fucose incorporation rate reached the maximum observed for any age studied. This developmental pattern seems to be related to the ontogenesis of dopamine receptor sites or dopamine sensitive adenylate cyclase formation in this brain structure. In the hippocampus the postnatal development of dopamine induced augmentation of glycoprotein synthesis showed a longer latency, but the maximum effect was also seen in 30 day old animals. These results support our assumption that at the end of the postnatal differentiation period the glycoprotein synthesis in brain tissue may be controlled (at least to some extent) by the state of dopaminergic receptors and/or of dopamine sensitive adenylate cyclase.

B. Lössner

Papers

Dopamine and macromolecule synthesis in rat hippocampus

Hippocampal activation and incorporation of macromolecule precursors

Apomorphine and glycoprotein synthesis in rat hippocampus

The influence of dopamine on the incorporation of different sugars into total proteins of hippocampal slices

Dopamine induced changes in L-fucose incorporation into proteins of rat hippocampus and corpus striatum during postnatal development.