Skip to main content

Advertisement

Log in

Nicotine sensitization in adult male and female rats quinpirole-primed as neonates

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Increases in dopamine D2-like receptor function are common in several psychological disorders that demonstrate a four to five fold increase in nicotine abuse compared to the general population.

Objective

The objective of this study was to analyze the interaction of sex differences and sensitization to nicotine in rats D2 receptor primed as neonates.

Materials and methods

A total of 32 male and 32 female Sprague-Dawley rats derived from eight litters were ontogenetically treated with quinpirole (1 mg/kg) or saline from postnatal days (P) 1–21 and raised to adulthood. At P60, all animals were given an acute injection of quinpirole HCl (100 μg/kg) and yawns were counted for 1 h. Yawning has been shown to be a behavioral event mediated by D2-like receptors. Beginning on P61–65, animals were habituated to a locomotor arena and subsequently administered either nicotine (0.5 mg/kg free base) or saline (intraperitoneal) every second day for 3 weeks. Approximately 15 min after each injection, animals were placed into the arena and horizontal activity and vertical rears were recorded.

Results

A robust increase of yawning was observed at P60 in D2 primed as compared to saline controls. Priming of D2-like receptors increased the locomotor response to nicotine in horizontal activity in both males and females, but females demonstrated a more robust hypoactive locomotor response to initial nicotine treatment when compared to saline-treated females. Nicotine also produced a significant decrease of vertical rearing in both males and females.

Conclusions

It appears that D2 receptor priming enhances sensitization to nicotine in adult rats, and females may be more behaviorally sensitive to nicotine than males.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Abi-Dargham A, Gil R, Krystal J, Baldwin RM, Seibyl JP, Bowers M, van Dyck CH, Charney DS, Innis RB, Laruelle M (1998) Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am J Psychiatry 155:761–767

    PubMed  CAS  Google Scholar 

  • Balfour DJ (2004) The neurobiology of tobacco dependence: a preclinical perspective on the role of the dopamine projections to the nucleus accumbens. Nicotine Tob Res 6:899–891

    Article  PubMed  CAS  Google Scholar 

  • Balfour DJ, Benwell ME, Birrell CE, Kelly RJ, Al-Aloul M (1998) Sensitization of the mesoaccumbens dopamine response to nicotine. Pharmacol Biochem Behav 59:1021–1030

    Article  PubMed  CAS  Google Scholar 

  • Battig K (1981) Smoking and the behavioral effects of nicotine. Trends Pharmacol Sci 2:145–147

    Article  Google Scholar 

  • Belluzzi JD, Lee AG, Oliff HS, Leslie FM (2004) Age-dependent effects of nicotine on locomotor activity and conditioned place preference in rats. Psychopharmacology 174:389–9

    Article  PubMed  CAS  Google Scholar 

  • Booze RM, Welch MA, Wood ML, Billings KA, Apple SR, Mactutus CF (1999) Behavioral sensitization following repeated intravenous nicotine administration: gender differences and gonadal hormones. Pharmacol Biochem Behav 64:827–839

    Article  PubMed  CAS  Google Scholar 

  • Brown RW, Gass JT, Kostrzewa RM (2002) Ontogenetic quinpirole treatments produce spatial memory deficits and enhance skilled reaching in adult rats. Pharmacol Biochem Behav 72:591–600

    Article  PubMed  CAS  Google Scholar 

  • Brown RW, Thompson KN, Click IA, Best RA, Thacker SK, Perna MK (2005) The effects of eticlopride on Morris water task performance in male and female rats neonatally treated with quinpirole. Psychopharmacology 180:234–240

    Article  PubMed  CAS  Google Scholar 

  • Brown RW, Perna MK, Schaefer TL, Williams MT (2006) The effects of adulthood nicotine treatment on D2-mediated behavior and neurotrophins of rats neonatally treated with quinpirole. Synapse 59:253–259

    Article  PubMed  CAS  Google Scholar 

  • Campbell KM, McGrath MJ, Burton FH (1999) Differential response of cortical–limbic neuropotentiated compulsive mice to dopamine D1 and D2 receptor antagonists. Eur J Pharmacol 371:103–111

    Article  PubMed  CAS  Google Scholar 

  • Clarke PBS, Fu DS, Jakubovic A, Fibiger HC (1988) Evidence that mesolimbic dopaminergic activation underlies the locomotor stimulant action of nicotine in rats. J Pharmacol Exp Ther 246:701–708

    PubMed  CAS  Google Scholar 

  • Collins GT, Witkin JM, Newman AH, Svensson KA, Grundt P, Cao J, Woods JH (2005) Dopamine agonist-induced yawning in rats: a dopamine D3 receptor-mediated behavior. J Pharmacol Exp Ther 314:310–319

    Article  PubMed  CAS  Google Scholar 

  • Cooper SJ, Rusk N, Barber DJ (1989) Yawning induced by the selective dopamineD2 agonist N-0437 is blocked by the selective dopamine autoreceptor antagonist (+)-UH 232. Physiol Behav 45:1263–1266

    Article  PubMed  CAS  Google Scholar 

  • Corrigall WA, Franklin KJB, Coen KM, Clarke PBS (1992) The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine. Psychopharmacology 107:285–289

    Article  PubMed  CAS  Google Scholar 

  • Fu Y, Matta SG, Gao W, Sharp BM (2000) Local alpha-bungarotoxin-sensitive nicotinic receptors in the nucleus accumbens modulate nicotine-stimulated dopamine secretion in vivo. Neuroscience 101:369–375

    Article  PubMed  CAS  Google Scholar 

  • Harrod SB, Mactutus CF, Bennett K, Hasselrot U, Wu G, Welch M, Booze RM (2004) Sex differences and repeated intravenous nicotine: behavioral sensitization and dopamine receptors. Pharmacol Biochem Behav 78:581–592

    Article  PubMed  CAS  Google Scholar 

  • Holson RR, Pearce B (1992) Principles and pitfalls in the analysis of prenatal treatment effects in multiparous species. Neurotoxicol Teratol 14:221–228

    Article  PubMed  CAS  Google Scholar 

  • Jacobsen LK, D’Souza DC, Mencl WE, Pugh KR, Skudlarski P, Krystal JH (2004) Nicotine effects on brain function and functional connectivity in schizophrenia. Biol Psychiatry 55:850–858

    Article  PubMed  CAS  Google Scholar 

  • Jerome A, Sanberg PR (1987) The effects of nicotine on locomotor behavior in non-tolerant rats: a multivariate assessment. Psychopharmacol 1987:397–400

    Google Scholar 

  • Jimerson DC (1987) Role of dopamine mechanism in affective disorders. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven, New York, pp 505–511

    Google Scholar 

  • Kalivas PW, Sorg BA, Hooks MS (1993) The pharmacology and neural circuitry of sensitization to psychostimulants. Behav Pharmacol 4:315–334

    Article  PubMed  CAS  Google Scholar 

  • Kieling C, Roman T, Doyle AE, Hutz MH, Rohde LA (2006) Association between DRD4 gene and performance of children with ADHD in a test of sustained attention. Biol Psychiatry 60:1163–1165

    Article  PubMed  CAS  Google Scholar 

  • Kostrzewa RM (1995) Dopamine receptor supersensitivity. Neurosci Biobehav Rev 19:1–17

    Article  PubMed  CAS  Google Scholar 

  • Kostrzewa RM, Brus R (1991) Ontogenic homologous supersensitization of quinpirole-induced yawning in rats. Pharmacol Biochem Behav 39:517–519

    Article  PubMed  CAS  Google Scholar 

  • Kostrzewa RM, Brus R, Rykaczewska M, Plech A (1993) Low-dose quinpirole ontogenically sensitizes to quinpirole-induced yawning in rats. Pharmacol Biochem Behav 44:487–489

    Article  PubMed  CAS  Google Scholar 

  • Ksir C (1994) Acute and chronic nicotine effects on measures of activity in rats: a multivariate analysis. Psychopharmacol 115:105–109

    Article  CAS  Google Scholar 

  • Kumari V, Soni W, Sharma T (2001) Influence of cigarette smoking on prepulse inhibition of the acoustic startle response in schizophrenia. Hum Psychopharmacol 16:321–323

    Article  PubMed  Google Scholar 

  • Laruelle M, Abi-Dargham A, van Dyck CH, Gil R, D’Souza CD, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS, Innis RB (1996) Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc Natl Acad Sci U S A 93:9235–9240

    Article  PubMed  CAS  Google Scholar 

  • Laruelle M, Abi-Dargham A, Gil R, Kegeles L, Innis R (1999) Increased dopamine transmission in schizophrenia: relationship to illness phase. Biol Psychiatry 46:56–72

    Article  PubMed  CAS  Google Scholar 

  • Lasser K, Boyd JW, Woolhander S, Himmelstein D, McCormick D, Bor DH (2000) Smoking and mental illness: a population-based prevalence study. J Am Med Assoc 284:2606–2661

    Article  CAS  Google Scholar 

  • LeDuc PA, Mittleman G (1995) Schizophrenia and psychostimulant abuse: a review and re-analysis of clinical evidence. Psychopharmacology 121:407–427

    Article  PubMed  CAS  Google Scholar 

  • Levin ED, Rezvani AH (2006) Nicotinic–antipsychotic drug interactions and cognitive function. EXS 98:185–205

    PubMed  CAS  Google Scholar 

  • Maple AM, Perna MK, Parlaman JP, Stanwood GD, Brown RW (2007) Ontogenetic quinpirole treatment produces long-lasting decreases in the expression of Rgs9, but increases Rgs17 in the striatum, nucleus accumbens and frontal cortex. Eur J Neurosci 26:2532–2538

    Article  PubMed  Google Scholar 

  • Marcondes FK, Bianchi FJ, Tanno AP (2002) Determination of the estrous cycle phases of rats: some helpful considerations. Braz J Biol 62:609–614

    Article  PubMed  CAS  Google Scholar 

  • Marshall DL, Redfern PH, Wonnacott S (1997) Presynaptic nicotinic modulation of dopamine release in the three ascending pathways studied by in vivo microdialysis: comparison of naive and chronic nicotine-treated rats. J Neurochem 68:1511–1519

    Article  PubMed  CAS  Google Scholar 

  • Miyata G, Meguid MM, Varma M, Fetissov SO, Kim HJ (2001) Nicotine alters the usual reciprocity between meal size and meal number in female rat. Physiol Behav 74:169–176

    Article  PubMed  CAS  Google Scholar 

  • Nisell M, Nomikos GG, Svensson TH (1994) Infusion of nicotine in the ventral tegmental area or the nucleus accumbens of the rat differentially affects accumbal dopamine release. Pharmacol Toxicol 75:348–352

    Article  PubMed  CAS  Google Scholar 

  • Nowak P, Brus R, Kostrzewa RM (2001) Amphetamine-induced enhancement of neostriatal in vivo microdialysate dopamine content in rats, quinpirole-primed as neonates. Pol J Pharm 53:319–329

    CAS  Google Scholar 

  • Olincy A, Harris JG, Johnson LL, Pender V, Kongs S, Allensworth D, Ellis J, Zerbe GO, Leonard S, Stevens KE, Stevens JO, Martin L, Adler LE, Soti F, Kem WR, Freedman R (2006) Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia. Arch Gen Psychiatry 63:630–638

    Article  PubMed  CAS  Google Scholar 

  • Robinson TE, Berridge KC (1993) Neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev 18:247–291

    Article  PubMed  CAS  Google Scholar 

  • Rosecrans JA (1971) Effects of nicotine on behavioral arousal and brain 5-hydroxytryptamine function in female rats selected for differences in activity. Eur J Pharmacol 14:29–37

    Article  PubMed  CAS  Google Scholar 

  • Rosecrans JA (1972) Brain area nicotine levels in male and female rats with different levels of spontaneous activity. Neuropharmacology 11:863–870

    Article  PubMed  CAS  Google Scholar 

  • Samaha AN, Robinson TE (2005) Why does the rapid delivery of drugs to the brain promote addiction? Trends Pharmacol Sci 26:82–87

    Article  PubMed  CAS  Google Scholar 

  • Schindler CW, Carmona GN (2002) Effects of dopamine agonists and antagonists on locomotor activity in male and female rats. Pharmacol Biochem Behav 72:857–863

    Article  PubMed  CAS  Google Scholar 

  • Seeman P, Schwarz J, Chen JF, Szechtman H, Perreault M, McKnight GS, Roder JC, Quirion R, Boksa P, Srivastava LK, Yanai K, Weinshenker D, Sumiyoshi T (2006) Psychosis pathways converge via D2high dopamine receptors. Synapse 60:319–4

    Article  PubMed  CAS  Google Scholar 

  • Seeman P, Ko F, Jack E, Greenstein R, Dean B (2007) Consistent with dopamine supersensitivity, RGS9 expression is diminished in the amphetamine-treated animal model of schizophrenia and in postmortem schizophrenia brain. Synapse 61:303–309

    Article  PubMed  CAS  Google Scholar 

  • Sery O, Drtilkova I, Theiner P, Pitelova R, Staif R, Znojil V, Lochman J, Didden W (2006) Polymorphism of DRD2 gene and ADHD. Neuro Endocrinol Lett 27:236–240

    PubMed  CAS  Google Scholar 

  • Snyder M (2006) Serious mental illness and smoking cessation. Issues Ment Health Nurs 27:635–645

    Article  PubMed  Google Scholar 

  • Stolerman IP (1991) Behavioural pharmacology of nicotine: multiple mechanisms. Br J Addict 86:533–536

    Article  PubMed  CAS  Google Scholar 

  • Szumlinski KK, Goodwill AM, Szechtman H (2000) Locomotor sensitization to quinpirole in rats: effects of drug abstinence and sex. Psychopharmacology 152:304–311

    Article  PubMed  CAS  Google Scholar 

  • Tammimaki A, Pietila K, Raattamaa H, Ahtee L (2006) Effect of quinpirole on striatal dopamine release and locomotor activity in nicotine-treated mice. Eur J Pharmacol 531:118–125

    Article  PubMed  CAS  Google Scholar 

  • Thacker SK, Perna MK, Ward JJ, Schaefer TL, Williams MT, Kostrzewa RM, Brown RW (2006) The effects of adulthood olanzapine treatment on cognitive performance and neurotrophic factor content in male and female rats neonatally treated with quinpirole. Eur J Neurosci 24:2075–2083

    Article  PubMed  Google Scholar 

  • Tizabi Y, Copeland RL Jr, Brus R, Kostrzewa RM (1999) Nicotine blocks quinpirole-induced behavior in rats: psychiatric implications. Psychopharmacology 145:433–441

    Article  PubMed  CAS  Google Scholar 

  • Ziedonis D, Williams JM, Smelson D (2003) Serious mental illness and tobacco addiction: a model program to address this common but neglected issue. Am J Med Sci 326:223–230

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Russell W. Brown.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Perna, M.K., Cope, Z.A., Maple, A.M. et al. Nicotine sensitization in adult male and female rats quinpirole-primed as neonates. Psychopharmacology 199, 67–75 (2008). https://doi.org/10.1007/s00213-008-1128-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-008-1128-5

Keywords

Navigation