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Lack of self-administration and behavioural sensitisation to morphine, but not cocaine, in mice lacking NK1 receptors

journal contribution
posted on 2023-06-07, 17:58 authored by Tamzin Ripley, Christopher A Gadd, Carmen De Filipe, Stephen P Hunt, David N Stephens
Mice lacking the NK1 receptor, the preferred receptor for substance P, demonstrate normal analgesic responses to morphine on the hot plate assay, but have been predicted, on the basis of conditioned place preference studies, to be insensitive to the rewarding properties of opiates. In this study, self-administration and the development and maintenance of locomotor sensitisation of both morphine and cocaine were investigated in mice that lacked the NK1 gene (NK1 knockout mice, NK1-/-). Both wildtype and NK1-/- mice learned an operant lever-press response to obtain food. When intravenous infusions of morphine (0.2 mg/kg/infusion) were substituted for the food reward, the wildtype mice initially reduced rates of lever pressing, but then increased them on the rewarded lever to obtain approx. 10 infusions per 90 min session; in contrast, NK1-/- mice continued to operate both the rewarded, and non-rewarded levers at low rates. Additionally, NK1-/- mice failed, following repeated administration, to sensitise to the locomotor stimulant effects of morphine (15 mg/kg, i.p.). These deficits were specific to opiates, since NK1-/- mice responding for food or cocaine self-administration (0.65 mg/kg/infusion) did not differ from wildtypes, and they showed normal behavioural sensitisation to repeated cocaine administration (10 mg/kg, i.p.). These results demonstrate that NK1 receptors are critical for the reinforcing properties of morphine, and for adaptive responses elicited by repeated opiate administration. It is postulated that substance P and the NK1 receptor may be necessary for the development of opiate, but not cocaine addiction.

History

Publication status

  • Published

Journal

Neuropharmacology

ISSN

0028-3908

Publisher

Elsevier

Issue

8

Volume

43

Page range

1258-1268

Department affiliated with

  • Psychology Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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