Age-dependent Effects of Dopamine on Working Memory and Synaptic Plasticity in Hippocampal CA3-CA1 Synapses in Mice.

Normal aging in mammals is accompanied by a decline in learning and memory. Dopamine plays a vital role in regulating cognitive functions, but it declines with age: During non-pathological aging, dopamine levels, receptors, and transporters decrease. Regarding the role of the dopaminergic system's changes in old age, we examined the effect of age and applied dopamine on working memory, synaptic transmission, and long-term potentiation (LTP) induction and maintenance in young adult and mature adult mice. We employed the Y-maze spontaneous alteration test to evaluate working memory. Maturation had no observed effect on working memory performance. Interestingly, working memory performance increased following intracerebroventricular administration of dopamine only in mature adult mice. We employed evoked field potential recording (in vitro) to assess the effects of age and maturation on the long-term potentiation (LTP) induction and maintenance. There was no difference in LTP induction and maintenance between young and mature adult mice before dopamine application. However, the application of dopamine on mature adult murine slices increased LTP magnitude compared to slices from young adults. According to the obtained results, it may be concluded that hippocampal neural excitability increased in mature adult subjects, and application of dopamine abolished the difference in neural excitability among young mature and adult mature groups; which was accompanied with increment of working memory and synaptic potentiation in mature adult animals.

Microinjection of the mGluR5 antagonist MTEP into the nucleus accumbens attenuates the acquisition but not expression of morphine-induced conditioned place preference in rats.

Previous studies suggest that metabotropic glutamate receptor type 5 (mGluR5) plays an important role in modulation of the rewarding properties of morphine. Little is known about the role of mGluR5 in the nucleus accumbens (NAc), as one of the important regions of the reward circuitry. In the present study, we investigated the effects of intra-accumbal injection of mGluR5 antagonist, 3-[(2-methyl-4-thiazolyl) ethynyl] pyridine, MTEP, on the acquisition and expression of morphine induced Conditioned Place Preference (CPP) in the rats. Eighty four adult male Wistar rats (220-260g) were bilaterally implanted with cannulae into the NAc. Subjects were tested in a CPP paradigm. Different doses of MTEP (0.3, 1 and 3µg/0.5µl per side) were delivered bilaterally into NAc during 3 conditioning days (Acquisition) or post-conditioning day (Expression). Results showed that bilateral intra accumbal administration of MTEP (1 and 3µg) significantly attenuated the acquisition but not expression of morphine-induced CPP in a dose-dependent manner. Our findings indicated that blockade of mGluR5 reduces rewarding properties of morphine. Further studies are needed to know the involved mechanisms.