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Nicotine and clozapine actions on pre-pulse inhibition deficits caused by N-methyl-D-aspartate (NMDA) glutamatergic receptor blockade.

Publication ,  Journal Article
Levin, ED; Petro, A; Caldwell, DP
Published in: Prog Neuropsychopharmacol Biol Psychiatry
May 2005

Pre-pulse inhibition (PPI) is a phenomenon of neurobehavioral plasticity in which the motor response to a startling stimulus is inhibited by a preceding stimulus of a lower intensity. Most often this is tested in the auditory mode. PPI is impaired in a variety of clinical states, most notably schizophrenia. PPI is easily modeled in experimental animals and serves as a useful basis for determining the neural bases for behavioral plasticity. In the current study we examined the interactions of N-methyl-D-aspartate (NMDA) glutamate and nicotinic cholinergic receptor systems in the expression of PPI. Female Sprague-Dawley rats were tested for auditory PPI after s.c. injections of the NMDA antagonist dizocilpine (also known as MK-801), the prototypic nicotinic agonist nicotine or both. Vehicle (saline) injections served as the control. Nicotine (0.2-0.8 mg/kg) by itself caused a modest but significant dose-related improvement in PPI. Dizocilpine (25-100 microg/kg) caused a dramatic dose-related impairment in PPI. Interestingly, the low to moderate doses of nicotine potentiated the PPI impairment by dizocilpine. In a second experiment nicotine and dizocilpine interactions with the atypical antipsychotic drug clozapine were assessed. As in the first experiment, nicotine potentiated the adverse effects of dizocilpine on PPI. The combination of nicotine with clozapine effectively attenuated the PPI impairment caused by dizocilpine when neither alone was effective. Inasmuch as PPI is impaired in schizophrenia, its reversal by the antipsychotic drug clozapine may depend on co-administration of nicotine by smoking in the patients. Development of nicotinic-based co-treatments for schizophrenia may achieve this benefit of nicotine without the hazards of smoking. Sensory modulation deficit, which is a syndrome of sensory over-responsiveness may also benefit from such combination therapy.

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Published In

Prog Neuropsychopharmacol Biol Psychiatry

DOI

ISSN

0278-5846

Publication Date

May 2005

Volume

29

Issue

4

Start / End Page

581 / 586

Location

England

Related Subject Headings

  • Reflex, Startle
  • Receptors, N-Methyl-D-Aspartate
  • Rats, Sprague-Dawley
  • Rats
  • Psychiatry
  • Nicotinic Agonists
  • Nicotine
  • Female
  • Excitatory Amino Acid Antagonists
  • Drug Synergism
 

Citation

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ICMJE
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Levin, E. D., Petro, A., & Caldwell, D. P. (2005). Nicotine and clozapine actions on pre-pulse inhibition deficits caused by N-methyl-D-aspartate (NMDA) glutamatergic receptor blockade. Prog Neuropsychopharmacol Biol Psychiatry, 29(4), 581–586. https://doi.org/10.1016/j.pnpbp.2005.01.012
Levin, Edward D., Ann Petro, and D Patrick Caldwell. “Nicotine and clozapine actions on pre-pulse inhibition deficits caused by N-methyl-D-aspartate (NMDA) glutamatergic receptor blockade.Prog Neuropsychopharmacol Biol Psychiatry 29, no. 4 (May 2005): 581–86. https://doi.org/10.1016/j.pnpbp.2005.01.012.
Levin ED, Petro A, Caldwell DP. Nicotine and clozapine actions on pre-pulse inhibition deficits caused by N-methyl-D-aspartate (NMDA) glutamatergic receptor blockade. Prog Neuropsychopharmacol Biol Psychiatry. 2005 May;29(4):581–6.
Levin, Edward D., et al. “Nicotine and clozapine actions on pre-pulse inhibition deficits caused by N-methyl-D-aspartate (NMDA) glutamatergic receptor blockade.Prog Neuropsychopharmacol Biol Psychiatry, vol. 29, no. 4, May 2005, pp. 581–86. Pubmed, doi:10.1016/j.pnpbp.2005.01.012.
Levin ED, Petro A, Caldwell DP. Nicotine and clozapine actions on pre-pulse inhibition deficits caused by N-methyl-D-aspartate (NMDA) glutamatergic receptor blockade. Prog Neuropsychopharmacol Biol Psychiatry. 2005 May;29(4):581–586.
Journal cover image

Published In

Prog Neuropsychopharmacol Biol Psychiatry

DOI

ISSN

0278-5846

Publication Date

May 2005

Volume

29

Issue

4

Start / End Page

581 / 586

Location

England

Related Subject Headings

  • Reflex, Startle
  • Receptors, N-Methyl-D-Aspartate
  • Rats, Sprague-Dawley
  • Rats
  • Psychiatry
  • Nicotinic Agonists
  • Nicotine
  • Female
  • Excitatory Amino Acid Antagonists
  • Drug Synergism