Blockade of ventral pallidal opioid receptors induces a conditioned place aversion and attenuates acquisition of cocaine place preference in the rat

doi:10.1016/S0306-4522(03)00121-0

Neuroscience

Volume 119, Issue 1, 18 June 2003, Pages 241-249

https://doi.org/10.1016/S0306-4522(03)00121-0 Get rights and content

Abstract

Peripheral administration of naloxone is known to produce a conditioned place aversion and to block cocaine-induced conditioned place preference. The ventral pallidum receives a dense enkephalinergic projection from the nucleus accumbens and is implicated as a locus mediating the rewarding and reinforcing effects of psychostimulant and opiate drugs. We sought to provide evidence for the involvement of pallidal opioid receptors in modulating affective state using the place-conditioning paradigm. Microinjection of naloxone (0.01–10 μg) into the ventral pallidum once a day for 3 days dose-dependently produced a conditioned place aversion when tested in the drug-free state 24 h after the last naloxone injection. This effect was reproduced using the μ-opioid receptor selective agonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH₂ (CTOP, 1 μg). Locomotor activity was reduced following injection of the highest dose of naloxone (10 μg) but elevated following CTOP (1 μg). Daily injection of cocaine (10 mg/kg) for 3 days produced a conditioned place preference 24 h later. This effect of cocaine was attenuated by concomitant intra-ventral pallidal injection of naloxone at a dose (0.01 μg) that had no significant aversive property when injected alone. In contrast, the locomotor activation induced by peripheral cocaine injection was unaffected by naloxone injection into the ventral pallidum.

The data implicate endogenous opioid peptide systems within the ventral pallidum as regulators of hedonic status.

Section snippets

Subjects

Adult male Sprague–Dawley rats obtained from Harlan (Indianapolis, IN, USA) (175–225 g) were handled and weighed daily for 5 days prior to the start of the experiment. Subjects were housed in groups of two or three in transparent (9×19×8 cm) plastic cages and received food and standard laboratory rat chow ad libitum. The colony was maintained on a 12-h light/dark cycle, lights on 0800–2000 h at an ambient temperature of 68–70 °C. All experiments were carried out in accordance with the National

Experiment 1

Analysis of habituation data showed no preconditioning bias for either conditioning chamber across all animals (F_1,100=0.642; P>0.05) (data not shown). Moreover, after random allocation to drug-treatment groups, time spent in the future drug-paired chamber during the habituation period was balanced across the five treatment groups (vehicle, naloxone 0.01, 0.1,1, 10 μg) (F_4,46=0.279; P>0.05; data not shown).

Intra-VP naloxone produced a dose-dependent aversion (Fig. 1A). Statistical analysis of

Discussion

We have demonstrated that microinjection of the general opioid antagonist, naloxone, into the VP dose-dependently induces a CPA in rats. This effect appears to involve the μ-opioid receptor, as the selective μ antagonist, CTOP, administered locally into this region, was similarly able to produce a CPA. Furthermore, pretreatment with ventral pallidal injection of naloxone, at a dose that alone did not produce aversion, blocked the acquisition of cocaine CPP, without affecting cocaine-induced

Acknowledgments

We would like to acknowledge Drs. Chris Evans, Bernard Balleine, Michael Fanselow, Kabir Lutfy and Shridhar Narayanan for helpful discussions. We’re grateful to Terry Novorr and Grace Leon for administrative assistance. Supported in part by NIDA grants DA09359 and DA05010; P.D.S. was supported by a NIDA training grant T32DA07272 and the Hatos Research Center for Neuropharmacology.

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Research paperBlockade of ventral pallidal opioid receptors induces a conditioned place aversion and attenuates acquisition of cocaine place preference in the rat

Abstract

Section snippets

Subjects

Experiment 1

Discussion

Acknowledgments

Life Sci

Pharmacol Biochem Behav

Pharmacol Biochem Behav

Eur J Pharmacol

Neuroscience

Brain Res

Brain Res

Neuroscience

Neuroscience

Brain Res

Brain Res

Drug Alcohol Depend

Brain Res

Neuropharmacology

Brain Res

Neuropharmacology

Behav Brain Res

Neuroscience

Biol Psychiatry

Eur J Pharmacol

Trends Neurosci

J Chem Neuroanat

Trends Neurosci

Neuroscience

Neuropsychopharmacology

Eur J Pharmacol

Pharmacol Biochem Behav

Brain Res

Brain Res

Neuropharmacology

Neuroscience

Neuroscience

Neuropharmacology

Behav Brain Res

Pharmacol Biochem Behav

Brain Res Bull

Eur Neuropsychopharmacology

Pharmacol Biochem Behav

Brain Res

Behav Brain Res

Brain Res

Neuroscience

Research paper
Blockade of ventral pallidal opioid receptors induces a conditioned place aversion and attenuates acquisition of cocaine place preference in the rat