Elsevier

Brain Research

Volume 769, Issue 1, 19 September 1997, Pages 119-124
Brain Research

Research report
Augmentation of LTP induced by Primed–Bursts tetanic stimulation in hippocampal CA1 area of morphine dependent rats

https://doi.org/10.1016/S0006-8993(97)00608-2Get rights and content

Abstract

The effects of chronic morphine administration on the development of Long-term potentiation (LTP) were investigated at the Schaffer collateral-CA1 pyramidal cell synapses of the rat hippocampal slices using primed-bursts tetanic stimulation. Significant enhancement of orthodromic population spike (OPS) was found for all stimulus intensities after tetanic stimulation. OPS enhancement was greatest when tested with low to mid-range stimulus intensities (25 and 50 μA). There was also significant decrease in OPS delay. These responses were similar in slices from both control and morphine dependent rats. At all delivered stimulus intensities, the amount of LTP of OPS in slices from dependent rats was larger than that of control slices. However, these differences in LTP of OPS were significant at low stimulus intensities. These findings suggest that chronic morphine administration had induced changes in CA1 neurocircuitry which modulated synaptic plasticity during high frequency stimulation and appeared as augmented LTP.

Introduction

The presence of proenkephalin and prodynorphine-derived opioid peptides and different opioid receptor subtypes has been demonstrated in different regions including CA1 area of rat hippocampus 7, 10, 20. It is generally accepted that exogenously applied opioids, through different subtypes of opioid receptors, induce predominantly excitatory responses of the principal neurons in three major hippocampal regions 7, 12, 16, 19, 20, 25.

Long-term potentiation is an enduring change in synaptic efficacy that results from high frequency afferent stimulation 4, 11. It has been suggested that synaptic plasticity is influenced by endogenous opioids [8]. Few studies have addressed the question of whether naloxone affects the synaptic transmission during high frequency stimulation of opioid containing pathways. It has been reported that naloxone impairs induction of LTP in lateral perforant path-dentate gyrus of anesthetized rat 5, 6. Xie and Lewis [28]reported opioid-mediated facilitation of LTP at the lateral perforant path-dentate granule cell synapses. The involvement of opioids in LTP of lateral perforant path-CA3 synapses, has also been reported 6, 17. Derrick and Martinez [8]showed the involvement of opioids in mossy fiber LTP induction. A study by Stringer et al. [23], showed that opiate agonist cyclozocine, attenuated LTP and morphine had no effect on the magnitude of LTP in CA1 region of hippocampal slices. They noted a reduction of LTP in the presence of morphine and ketocyclozocine in vivo. Linseman and Corrigall [15]reported that naloxone had no effects on the LTP of CA1 region. There are other reports about the effects of chronic morphine administration on the responsiveness of hippocampal pyramidal cells to the application of morphine and other opioids 22, 26. It has been reported that chronic morphine administration decreases the sensitivity of both early and late IPSP conductances to mu receptor agonists [27]and changes the activity of other neurotransmitter systems such as adrenergic pathways in hippocampus [2]. These findings suggested that endogenous opioids might modulate synaptic plasticity during high frequency stimulation, and so, chronic presence of exogenous opioids might affect these activities of endogenous opioid system or other neurotransmitter systems. However, the effects of chronic morphine administration on LTP induction had not been fully investigated.

Therefore, to investigate the effects of chronic morphine administration on LTP of CA1, we studied the production of LTP in hippocampal slices of chronically morphine treated rats.

Section snippets

Chronic morphine administration

Male NMRI rats (150–260 g) were housed three per cage at controlled temperature exposed to a controlled 12 h light–dark cycle. Rats were allowed access to morphine solution as their sole source of fluid, and food (pellets), ad libitum. Sucrose 3% w/v was added to morphine solution (tap water with morphine) to mask the bitter taste of morphine sulfate. Rats were made dependent by chronic administration of morphine 0.1 mg/ml, 0.2 mg/ml, 0.3 mg/ml each for 48 h and 0.4 mg/ml during the following

Test of dependence to morphine

Fig. 1, shows the results of withdrawal syndrome test, precipitated by naloxone. In our pilot study, morphine treated rats (n=8 from two separate groups) showed at least 5 withdrawal signs in which the diarrhea, writhing and weight loss were common. Time matched control rats (n=4) did not show any defined withdrawal signs.

Baseline recording

Electrical stimulation of the afferent fibers in the stratum radiatum, elicited a synchronous firing of the CA1 pyramidal cells that could be measured extracellularly (Fig. 2

Discussion

There are different protocols to induce tolerance and dependence to morphine such as daily i.p. injection [24]or using subcutaneous pellets [27]. In our experiment, morphine was administered in drinking water to avoid stress of handling and injection or surgical procedure of morphine pellet implantation. The development of dependence by this protocol of morphine administration was checked in our pilot study and all treated rats showed signs of the withdrawal syndrome. This model of dependence

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