Research reportAugmentation of LTP induced by Primed–Bursts tetanic stimulation in hippocampal CA1 area of morphine dependent rats
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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2014, European Journal of PharmacologyCitation Excerpt :The exact effect that activation of µ-opioid receptors has on synaptic plasticity in CA1 area was reported to depend on previous drug exposure. For example, it facilitated long term depression (Wagner et al., 2001) while morphine-dependent animals showed a facilitation of long-term potentiation (Mansouri et al., 1999, 1997). Opiate receptor activation was also shown to inhibit and controversially stimulate adenylyl cyclase activity and produce both analgesia and hyperalgesia (Kayan et al., 1971; Tilson et al., 1973).
Effects of voluntary exercise on hippocampal long-term potentiation in morphine-dependent rats
2014, NeuroscienceCitation Excerpt :The conflicts between these studies could be due to the fact that, different experimental protocols such as the pattern of stimulation, the time points of synaptic responses recording after the morphine injection, and the site of stimulation might be involved in the modulation of synaptic responses. For example, Pu et al. (2002) showed that chronic exposure of rats to morphine markedly reduced the capacity of hippocampal CA1 LTP during the period of drug withdrawal (9–12 h after the termination of chronic treatment), while Mansouri et al. (1997, 1999) demonstrated the augmented LTP in the Schalleral-CA1 synapses of the hippocampal slices taken from dependent, but not withdrawn rats. Many studies have assumed that abused drugs can hijack synaptic machinery that are dedicated to plastic changes in the excitability of principal hippocampus circuits (Robbins and Everitt, 1999; Wolf, 2002; Bao et al., 2007; Kauer and Malenka, 2007), and may induce maladaptive plasticity in this structure (Eisch et al., 2000).