Effects of cocaine, nicotine, dizocipline and alcohol on mice locomotor activity: Cocaine-alcohol cross-sensitization involves upregulation of striatal dopamine transporter binding sites

Yossef Itzhak, Julio L. Martin

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

We investigated if repeated administration of cocaine, nicotine, dizocipline (MK-801) and alcohol yields behavioral cross-sensitization between these agents. Swiss Webster mice received in their home cage one of the following intraperitoneal (i.p.) injections for 5 consecutive days: (a) saline, (b) cocaine (20 mg/kg), (c) nicotine (0.5 mg/kg), (d) MK-801 (0.3 mg/kg) and (e) ethanol (2.0 g/kg). After a 10-day drug free period, each group (n = 30) was divided into three subgroups (n = 10) and received challenge injections of either cocaine, nicotine or MK-801. The horizontal and vertical movements of the mice were recorded in locomotor activity cages (test cage). Among the various drugs tested, only the cocaine and ethanol experienced mice developed sensitization to a challenge injection of cocaine; MK-801 pretreated mice showed a sensitized response only to a challenge injection of MK-801. In a second experiment, mice in their home cages received (a) saline, (b) cocaine (20 mg/kg) or (c) ethanol (2.0 g/kg) for 5 days, and challenged with an i.p. ethanol injection (2.0 g/kg) after a 10- day drug free period. Both, cocaine and ethanol experienced mice developed marked sensitization to ethanol challenge compared with the saline experienced mice. Assessment of the densities of striatal dopamine transporter (DAT) sites (by [3H]mazindol binding) 11 days after the extinction of repeated treatment with either cocaine or ethanol revealed a significant increase (71-108%) in the number of DAT binding sites. Thus, among the various psychostimulants investigated in the present study cross- sensitization between cocaine and ethanol was only observed. The behavioral sensitization we measured was primarily 'drug-dependent', rather than 'context-dependent', because animals were exposed to the test cage only once. The finding that cocaine- and ethanol-induced behavioral sensitization is associated with upregulation of striatal DAT binding sites supports the hypothesis that similar neural substrates are involved in the psychomotor/rewarding effects of cocaine and alcohol.

Original languageEnglish
Pages (from-to)204-211
Number of pages8
JournalBrain Research
Volume818
Issue number2
DOIs
StatePublished - Feb 13 1999

Fingerprint

Corpus Striatum
Dopamine Plasma Membrane Transport Proteins
Locomotion
Nicotine
Cocaine
Up-Regulation
Binding Sites
Alcohols
Ethanol
Dizocilpine Maleate
Intraperitoneal Injections
Pharmaceutical Preparations
Injections
Mazindol

Keywords

  • Cocaine
  • Dizocipline
  • Dopamine transporter
  • Ethanol
  • Nicotine
  • Sensitization

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "Effects of cocaine, nicotine, dizocipline and alcohol on mice locomotor activity: Cocaine-alcohol cross-sensitization involves upregulation of striatal dopamine transporter binding sites",
abstract = "We investigated if repeated administration of cocaine, nicotine, dizocipline (MK-801) and alcohol yields behavioral cross-sensitization between these agents. Swiss Webster mice received in their home cage one of the following intraperitoneal (i.p.) injections for 5 consecutive days: (a) saline, (b) cocaine (20 mg/kg), (c) nicotine (0.5 mg/kg), (d) MK-801 (0.3 mg/kg) and (e) ethanol (2.0 g/kg). After a 10-day drug free period, each group (n = 30) was divided into three subgroups (n = 10) and received challenge injections of either cocaine, nicotine or MK-801. The horizontal and vertical movements of the mice were recorded in locomotor activity cages (test cage). Among the various drugs tested, only the cocaine and ethanol experienced mice developed sensitization to a challenge injection of cocaine; MK-801 pretreated mice showed a sensitized response only to a challenge injection of MK-801. In a second experiment, mice in their home cages received (a) saline, (b) cocaine (20 mg/kg) or (c) ethanol (2.0 g/kg) for 5 days, and challenged with an i.p. ethanol injection (2.0 g/kg) after a 10- day drug free period. Both, cocaine and ethanol experienced mice developed marked sensitization to ethanol challenge compared with the saline experienced mice. Assessment of the densities of striatal dopamine transporter (DAT) sites (by [3H]mazindol binding) 11 days after the extinction of repeated treatment with either cocaine or ethanol revealed a significant increase (71-108{\%}) in the number of DAT binding sites. Thus, among the various psychostimulants investigated in the present study cross- sensitization between cocaine and ethanol was only observed. The behavioral sensitization we measured was primarily 'drug-dependent', rather than 'context-dependent', because animals were exposed to the test cage only once. The finding that cocaine- and ethanol-induced behavioral sensitization is associated with upregulation of striatal DAT binding sites supports the hypothesis that similar neural substrates are involved in the psychomotor/rewarding effects of cocaine and alcohol.",
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T1 - Effects of cocaine, nicotine, dizocipline and alcohol on mice locomotor activity

T2 - Cocaine-alcohol cross-sensitization involves upregulation of striatal dopamine transporter binding sites

AU - Itzhak, Yossef

AU - Martin, Julio L.

PY - 1999/2/13

Y1 - 1999/2/13

N2 - We investigated if repeated administration of cocaine, nicotine, dizocipline (MK-801) and alcohol yields behavioral cross-sensitization between these agents. Swiss Webster mice received in their home cage one of the following intraperitoneal (i.p.) injections for 5 consecutive days: (a) saline, (b) cocaine (20 mg/kg), (c) nicotine (0.5 mg/kg), (d) MK-801 (0.3 mg/kg) and (e) ethanol (2.0 g/kg). After a 10-day drug free period, each group (n = 30) was divided into three subgroups (n = 10) and received challenge injections of either cocaine, nicotine or MK-801. The horizontal and vertical movements of the mice were recorded in locomotor activity cages (test cage). Among the various drugs tested, only the cocaine and ethanol experienced mice developed sensitization to a challenge injection of cocaine; MK-801 pretreated mice showed a sensitized response only to a challenge injection of MK-801. In a second experiment, mice in their home cages received (a) saline, (b) cocaine (20 mg/kg) or (c) ethanol (2.0 g/kg) for 5 days, and challenged with an i.p. ethanol injection (2.0 g/kg) after a 10- day drug free period. Both, cocaine and ethanol experienced mice developed marked sensitization to ethanol challenge compared with the saline experienced mice. Assessment of the densities of striatal dopamine transporter (DAT) sites (by [3H]mazindol binding) 11 days after the extinction of repeated treatment with either cocaine or ethanol revealed a significant increase (71-108%) in the number of DAT binding sites. Thus, among the various psychostimulants investigated in the present study cross- sensitization between cocaine and ethanol was only observed. The behavioral sensitization we measured was primarily 'drug-dependent', rather than 'context-dependent', because animals were exposed to the test cage only once. The finding that cocaine- and ethanol-induced behavioral sensitization is associated with upregulation of striatal DAT binding sites supports the hypothesis that similar neural substrates are involved in the psychomotor/rewarding effects of cocaine and alcohol.

AB - We investigated if repeated administration of cocaine, nicotine, dizocipline (MK-801) and alcohol yields behavioral cross-sensitization between these agents. Swiss Webster mice received in their home cage one of the following intraperitoneal (i.p.) injections for 5 consecutive days: (a) saline, (b) cocaine (20 mg/kg), (c) nicotine (0.5 mg/kg), (d) MK-801 (0.3 mg/kg) and (e) ethanol (2.0 g/kg). After a 10-day drug free period, each group (n = 30) was divided into three subgroups (n = 10) and received challenge injections of either cocaine, nicotine or MK-801. The horizontal and vertical movements of the mice were recorded in locomotor activity cages (test cage). Among the various drugs tested, only the cocaine and ethanol experienced mice developed sensitization to a challenge injection of cocaine; MK-801 pretreated mice showed a sensitized response only to a challenge injection of MK-801. In a second experiment, mice in their home cages received (a) saline, (b) cocaine (20 mg/kg) or (c) ethanol (2.0 g/kg) for 5 days, and challenged with an i.p. ethanol injection (2.0 g/kg) after a 10- day drug free period. Both, cocaine and ethanol experienced mice developed marked sensitization to ethanol challenge compared with the saline experienced mice. Assessment of the densities of striatal dopamine transporter (DAT) sites (by [3H]mazindol binding) 11 days after the extinction of repeated treatment with either cocaine or ethanol revealed a significant increase (71-108%) in the number of DAT binding sites. Thus, among the various psychostimulants investigated in the present study cross- sensitization between cocaine and ethanol was only observed. The behavioral sensitization we measured was primarily 'drug-dependent', rather than 'context-dependent', because animals were exposed to the test cage only once. The finding that cocaine- and ethanol-induced behavioral sensitization is associated with upregulation of striatal DAT binding sites supports the hypothesis that similar neural substrates are involved in the psychomotor/rewarding effects of cocaine and alcohol.

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KW - Dizocipline

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KW - Nicotine

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