Behavioural and Neurochemical Assessment of Heantos 4 on Preclinical Models of Morphine-DependenceCarine Dias1#, Soyon Ahn1#, Bonita Ma1, Tran Van Sung2 and Anthony G Phillips1*
- *Corresponding Author:
- Anthony G Phillips
Department of Psychiatry and Djavad Mowafaghian Centre for Brain Health
University of British Columbia, 3402-2215 Wesbrook Mall, Vancouver, BC, USA
E-mail: [email protected]
Received date: July 05, 2016; Accepted date: August 02, 2016; Published date: August 08, 2016
Citation: Dias C, Ahn S, Ma B, Sung TV, Phillips AG (2016) Behavioural and Neurochemical Assessment of Heantos 4 on Preclinical Models of Morphine-Dependence. J Addict Res Ther 7:292. doi:10.4172/2155-6105.1000292
Copyright: © 2016 Dias C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: Opiate addiction is characterized by compulsive drug use and severe withdrawal symptoms during abstinence. Heantos 4, an herbal pharmacotherapy recently approved for opiate withdrawal treatment in Vietnam, has shown anti-craving properties. The present study is the first preclinical assessment of the effects of Heantos 4 on opiate withdrawal and the rewarding properties of morphine, along with its action on a critical neural substrate of addiction, the mesolimbic dopamine (DA) system.
Methods: Rats received morphine treatments (10 mg/kg, i.p.) for seven days. On Day 8, Heantos 4 (100, 250 or 500 mg/kg, p.o.) was administered prior to naloxone (1 or 10 mg/kg, i.p.). Affective withdrawal symptoms were measured using conditioned place aversion (CPA) and somatic withdrawal symptoms were scored separately. The effect of Heantos 4 on morphine-induced (5 mg/kg, i.p.) conditioned place preference (CPP) was assessed by administering it prior to conditioning, expression or morphine-induced reinstatement. Additionally, the effect of Heantos 4 on the long-term maintenance of morphine-induced CPP was assessed bi-weekly for 6 weeks. Microdialysis studies assessed DA efflux in the nucleus accumbens of rats receiving one or seven repeated treatments of Heantos 4 (500 mg/kg, p.o.) and morphine, or receiving Heantos 4 and naloxone (10 mg/kg, i.p.).
Results: Heantos 4 reduced somatic but not affective components of naloxone-precipitated opiate withdrawal. It attenuated acquisition but not expression or reinstatement of morphine-induced CPP. Long-term maintenance of morphine-induced CPP was also reduced. Heantos 4 by itself enhanced DA efflux but blunted morphine-evoked DA release on Day 1 and 7. Heantos 4 attenuated naloxone-induced decrease in DA in morphine-dependent rats.
Conclusion: These findings demonstrate that Heantos 4 alleviates symptoms of somatic opiate withdrawal and indicate potential effects on incentive motivation. Moreover, Heantos 4 may modulate DA transmission that limits or antagonizes non-physiological fluctuations in mesolimbic DA activity induced by morphine and naloxone.