Blockade of mu-opioid receptors in the medial thalamus inhibits acquisition, but not expression, of morphine-induced conditioned place preference

doi:10.1016/j.neuroscience.2007.10.058

Neuroscience

Volume 151, Issue 4, 19 February 2008, Pages 948-954

https://doi.org/10.1016/j.neuroscience.2007.10.058 Get rights and content

Abstract

The medial thalamus contains abundant mu-opioid receptors and is activated by acute morphine administration. However, the role of the medial thalamus in the rewarding effects of morphine is unclear. The present study examined whether mu-opioid receptors of the medial thalamus influenced the acquisition and expression of morphine-induced conditioned place preference (CPP) in rats. An unbiased apparatus and biased subject assignment were used. Administration of morphine in increasing doses (2 mg/kg, 4 mg/kg, 6 mg/kg, 10 mg/kg, s.c.) was paired with an initially non-preferred chamber and saline administration was paired with an initially preferred chamber. Conditioning trials were conducted twice daily for 4 days. Microinjection of the irreversible mu-opioid receptor antagonist, β-funaltrexamine (5 μg/rat), into the medial thalamus 23 h prior to each morphine conditioning completely blocked the acquisition of CPP. However, microinjection of β-funaltrexamine into the medial thalamus after morphine conditioning trials, but 23 h prior to a test session, had no effect on the expression of CPP. It is concluded that mu-opioid receptors in the rat medial thalamus are involved in the acquisition, but not expression, of morphine-induced CPP.

Section snippets

Subjects

Male Sprague–Dawley rats (Charles River, Wilmington, MA, USA) weighing 225–250 g were housed in groups of two in transparent plastic cages with food and water ad libitum. Male rats were used in order to avoid the influence of estrogen on the rewarding effects of morphine (Carroll et al., 2004). Although a previous study found gender differences in morphine-induced CPP (Cicero et al., 2000), the differences did not appear at the doses that were used in the present study. The colony was

Results

Analysis of preconditioning data showed no significant difference in the percentage of time spent (mean±S.E.M.%) in the two distinct conditioning chambers across all animals (gray-wall chamber 48.75±0.91%, striped-wall chamber 51.25±0.91%, P=0.18, t=1.37, df=52), indicating no preconditioning bias for either specific chamber in the studied population of rats. Moreover, no significant differences in preference for either chamber were observed in experiment 1 (gray-wall chamber 48.62±1%,

Discussion

The major finding of this study is that administration of the mu-opioid receptor antagonist β-FNA into the medial thalamus prior to each morphine conditioning session completely blocked the acquisition of morphine-induced CPP (Fig. 1), whereas it had no effect when administered after morphine conditioning but before testing for place preference (Fig. 2). Our results indicate that mu-opioid receptors in the medial thalamus are required for the acquisition, but not expression, of morphine-induced

Conclusion

In summary, the current results show that inactivation of mu-opioid receptors in the medial thalamus blocks the acquisition, but not the expression, of morphine-induced CPP. Consistent with previous studies showing the involvement of the medial thalamus in reinforcement and reward (Gaffan and Murray 1990, Kawagoe et al 2007, McAlonan et al 1993, Mitchell and Dalrymple-Alford 2005, Oyoshi et al 1996), the present studies suggest that mu-opioid receptors in the medial thalamus contribute to the

Acknowledgments

This work was supported by HEF [2001-2007]-06 to R.E.H. and B.K.T. and by the VA and ONR (J.E.Z.).

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Behavioural neuroscienceBlockade of mu-opioid receptors in the medial thalamus inhibits acquisition, but not expression, of morphine-induced conditioned place preference

Abstract

Section snippets

Subjects

Results

Discussion

Conclusion

Acknowledgments

Neurosci Biobehav Rev

Brain Res

Trends Pharmacol Sci

Pharmacol Biochem Behav

Neuroscience

Neuroscience

Brain Res

Brain Res

Brain Res

Neuroscience

J Chem Neuroanat

Pharmacol Biochem Behav

Pharmacol Biochem Behav

Brain Res

Neuroscience

Trends Pharmacol Sci

Pharmacol Biochem Behav

Pharmacol Biochem Behav

Neurosci Lett

Prog Neurobiol

Brain Res Brain Res Rev

Cortex

Neuropsychologia

Eur J Pharmacol

Physiol Behav

Neurosci Lett

Neuroanatomical sites mediating the motivational effects of opioids as mapped by the conditioned place preference paradigm in rats

J Pharmacol Exp Ther

Conditioned place preference: what does it add to our preclinical understanding of drug reward?

Psychopharmacology (Berl)

Organization of the thalamostriatal projections in the rat, with special emphasis on the ventral striatum

J Comp Neurol

Behavioural neuroscience
Blockade of mu-opioid receptors in the medial thalamus inhibits acquisition, but not expression, of morphine-induced conditioned place preference