Abstract
Morphine administration causes long-lasting neural changes in the brain that underpin the behavioral abnormalities, and the relationship between structural changes and behavioral symptoms is obscure. In present study, the elevated plus-maze and transmission electron microscope were applied to validate the anxiety-like behaviors and synaptic ultrastructural changes in the hippocampi of rats among the morphine group (morphine administration only), the buspirone group (morphine plus buspirone administration) and the vehicle (saline treated only). As compared with the vehicle group, lower values of OE (times of entering into the open arms), OE% (percentage of entries into the open arms), OT (time spent in the open arms), OT% (percentage of time stayed in the open arms), Ns (surface density (Sv)/numerical density (Nv)) and S (surface area) of synapses were observed in the morphine group , but significantly, behavior higher scores of RR (rearing), HD (head-dipping), FBA (flat back approach), and higher Nv, Sv, PSD (postsynaptic density), LPT (length of postsynaptic thickening), WCJ (widths in synaptic cleft on junctions) and CCR (curvature of the cleft region) of synapses appeared in the morphine group. However, no significant differences in values of most of those parameters above were detected between the vehicle group and the buspirone group. These results supported that anxiety-like symptoms of rats significantly occurred to the rats after acute morphine withdrawal, but buspirone administration could reverse these indexes. It also proved that the appearance/disappearance of anxiety-related symptoms was related to the ultrastructural changes/reversibility of synapses in the hippocampus with morphine and buspirone administrations. So, it suggested that anxiety-related symptoms were modified in rats subjected to the synaptic ultrastructural changes in hippocampus by morphine acute withdrawal and were further rehabilitated by buspirone administration. It is helpful to pursue the effective therapeutic methods of morphine addiction.
Highlights
Chronic morphine administration can induce the changes of hippocampal CA1 neurocircuitry which modulate the synaptic plasticity through the regulation of long-term potentiation (LTP) and long-term depression (LTD) (Salmanzadeh et al, 2003)
Based on computer-recorded data, judgment of anxiety-like behaviors were validated by the following parameters for each rat: (1) times of rat entering into the open arms (OE); (2) the percentage of entries into the open arms as the total entries into both open and closed arms (OE%); (3) time spent in the open arms (OT); (4) the percentage of time stayed in the open arms as in both open and closed arms (OT%); (5) partial or total rising onto hind limbs; (6) exploratory movement of head/shoulders over the sides of the maze and down toward the floor (Head-dipping, HD); and (7) locomotion when the animal stretched to its full length and cautiously moves forward (Flat-back approach, FBA)
As compared with the saline group, lower values of OE, OE%, OT and OT% were observed in the morphine group (p < 0.01), but significantly, higher scores of RR, HD and FBA appeared in the morphine group (p < 0.01)
Summary
Chronic morphine administration can induce the changes of hippocampal CA1 neurocircuitry which modulate the synaptic plasticity through the regulation of long-term potentiation (LTP) and long-term depression (LTD) (Salmanzadeh et al, 2003). The synaptic plasticity is widely studied in hippocampal CA1 and CA3 fields, which is believed to be the mechanism underlying certain types of learning and memory (Moron et al, 2007). A potent anxiolytic compound in animal models (Riblet, et al, 1986), displays reversibility of synaptic activation of pyramidal cells in the hippocampus (Trulson et al.,1986; Mauk et al, 1988). It showed that buspirone bind selectively to presynaptic (dorsal raphe) and postsynaptic (hippocampus, cortex) 5-hydroxytryptamine 1A (5-HT1A) receptor binding sites, and the clinical trials of anxiety and depression may be related to the buspirone’s interactions with gepirone at pre-synaptic and postsynaptic 5-HT1A receptor (Yocca, 1990). Buspirone had no effect on the immediate rewarding properties of cocaine, but the attenuation of 5-HT neurotransmission (via the autoreceptor agonist properties of buspirone) could reverse the negative impact of cocaine (Ettenberg & Bernardi, 2007)
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