Skip to main content

Advertisement

SpringerLink
Log in

Effects of methamphetamine on sexual performance and compulsive sex behavior in male rats

  • original investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Methamphetamine (Meth) is a highly addictive psychostimulant associated with enhanced sexual desire, arousal, and sexual pleasure. Moreover, Meth abuse is frequently linked with the practice of sexual risk behavior and increased prevalence of human immunodeficiency virus. Currently, there is a lack of studies investigating the effects of Meth on maladaptive sexual behavior under controlled experimental settings in animal studies.

Objective

The overall objective of the current study was to examine the effects of Meth on various aspects of male sexual behavior including maladaptive sex-seeking behavior.

Methods

First, a dose–response curve of the effects of Meth (0, 1, 2, and 4 mg/kg; s.c.) on sexual motivation and performance was conducted in sexually naïve and experienced male rats. Next, the effects of Meth (1 mg/kg; s.c.) on inhibition of maladaptive sexual behavior was tested using a sex aversion conditioning paradigm, in which visceral illness induced by lithium chloride (LiCl) was paired with sexual behavior.

Results

Meth administration inhibited sexual performance in a dose-dependent matter as evidenced by the decreased percentages of males that mated and increased latencies to initiate sexual behavior when injected with 2 or 4 mg/kg Meth. Moreover, an acute dose of Meth prior to or following sex aversion conditioning resulted in disrupted conditioned inhibition of sexual behavior.

Conclusions

These data suggest that Meth administration in male rats impairs sexual motivation and performance. In addition, low doses of Meth that do not disrupt sexual function may result in maladaptive seeking of sexual behavior.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

CPP:

Conditioned place preference

E:

Ejaculation

EL:

Ejaculation latency

IL:

Intromission latency

IM:

Intromission

LiCl:

Lithium chloride

LAC:

Locomotor activity chamber

M:

Mount

Meth:

Methamphetamine

ML:

Mount latency

mPFC:

Medial prefrontal cortex

References

  • Agmo A (2002) Copulation-contingent aversive conditioning and sexual incentive motivation in male rats: evidence for a two-stage process of sexual behavior. Physiol Behav 77:425–435

    Article  CAS  PubMed  Google Scholar 

  • Agmo A (2003) Lack of opioid or dopaminergic effects on unconditioned sexual incentive motivation in male rats. Behav Neurosci 117:55–68

    Article  CAS  PubMed  Google Scholar 

  • Agmo A, Berenfeld R (1990) Reinforcing properties of ejaculation in the male rat: role of opioids and dopamine. Behav Neurosci 104:177–182

    Article  CAS  PubMed  Google Scholar 

  • Agmo A, Fernandez H (1989) Dopamine and sexual behavior in the male rat: a reevaluation. J Neural Transm 77:21–37

    Article  CAS  PubMed  Google Scholar 

  • Agmo A, Villalpando A (1995) Central nervous stimulants facilitate sexual behavior in male rats with medial prefrontal cortex lesions. Brain Res 696:187–193

    Article  CAS  PubMed  Google Scholar 

  • Bancroft J (2008) Sexual behavior that is “out of control”: a theoretical conceptual approach. Psychiatr Clin North Am 31:593–601

    Article  PubMed  Google Scholar 

  • Bell DS, Trethrowan WH (1961) Amphetamine addiction. J Nerv Ment Dis 133:489–496

    Article  CAS  PubMed  Google Scholar 

  • Bignami G (1966) Pharmacologic influences on mating behavior in the male rat. Effects of d-amphetamine, LSD-25, strychnine, nicotine and various anticholinergic agents. Psychopharmacologia 10:44–58

    Article  CAS  PubMed  Google Scholar 

  • Bolin BL, Akins CK (2009) Methamphetamine impairs sexual motivation but not sexual performance in male Japanese quail. Exp Clin Psychopharmacol 17:10–20

    Article  CAS  PubMed  Google Scholar 

  • Brewer JA, Potenza MN (2008) The neurobiology and genetics of impulse control disorders: relationships to drug addictions. Biochem Pharmacol 75:63–75

    Article  CAS  PubMed  Google Scholar 

  • Buffum J et al (1988) Street drugs and sexual function. In: Sisten JMA (Ed) Handbook of sexology. Elsevier Science. New York

  • Butcher LL, Butcher SG, Larsson K (1969) Effects of apomorphine, (+)-amphetamine, and nialamide on tetrabenazine-induced suppression of sexual behavior in the male rat. Eur J Pharmacol 7: 283–8

    Article  CAS  PubMed  Google Scholar 

  • Chapman DE, Hanson GR, Kesner RP, Keefe KA (2001) Long-term changes in basal ganglia function after a neurotoxic regimen of methamphetamine. J Pharmacol Exp Ther 296:520–527

    CAS  PubMed  Google Scholar 

  • Crowe LC, George WH (1989) Alcohol and human sexuality: review and integration. Psychol Bull 105:374–386

    Article  CAS  PubMed  Google Scholar 

  • Dalley JW, Cardinal RN, Robbins TW (2004) Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates. Neurosci Biobehav Rev 28:771–784

    Article  CAS  PubMed  Google Scholar 

  • Davis JF, Loos M, Di Sebastiano AR, Brown JL, Lehman MN, Coolen LM (2010) Lesions of the medial prefrontal cortex cause maladaptive sexual behavior in male rats. Biol Psychiatry 67:1199–1204

    Article  PubMed  Google Scholar 

  • Ellkashef A, Vocci F, Hanson G, White J, Wickes W, Tiihonen J (2008) Pharmacotherapy of methamphetamine addiction: an update. Subst Abuse 29:31–49

    Article  Google Scholar 

  • Everitt BJ, Robbins TW (2005) Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Neurosci 8:1481–1489

    Article  CAS  PubMed  Google Scholar 

  • Everitt BJ, Stacey P (1987) Studies of instrumental behavior with sexual reinforcement in male rats (Rattus norvegicus): II. Effects of preoptic area lesions, castration, and testosterone. J Comp Psychol 101:407–419

    Article  CAS  PubMed  Google Scholar 

  • Everitt BJ, Fray P, Kostarczyk E, Taylor S, Stacey P (1987) Studies of instrumental behavior with sexual reinforcement in male rats (Rattus norvegicus): I. Control by brief visual stimuli paired with a receptive female. J Comp Psychol 101:395–406

    Article  CAS  PubMed  Google Scholar 

  • Fineberg NA, Potenza MN, Chamberlain SR, Berlin HA, Menzies L, Bechara A, Sahakian BJ, Robbins TW, Bullmore ET, Hollander E (2009) Probing compulsive and impulsive behaviors, from animal models to endophenotypes: a narrative review. Neuropsychopharmacology 35:591–604

    Article  PubMed  Google Scholar 

  • Fisher DG, Reynolds GL, Ware MR, Napper LE (2009) Methamphetamine and viagra use: relationship to sexual risk behaviors. Arch Sex Behav (in press)

  • Friedman SD, Castañeda E, Hodge GK (1998) Long-term monoamine depletion, differential recovery, and subtle behavioral impairment following methamphetamine-induced neurotoxicity. Pharmacol Biochem Behav 61:35–44

    Article  CAS  PubMed  Google Scholar 

  • Frohmader KS, Pitchers KK, Balfour ME, Coolen LM (2010a) Mixing pleasures: review of the effects of drugs on sex behavior in humans and animal models. Horm Behav 58:149–162

    Article  CAS  PubMed  Google Scholar 

  • Frohmader KS, Wiskerke J, Wise RA, Lehman MN, Coolen LM (2010b) Methamphetamine acts on subpopulations of neurons regulating sexual behavior in male rats. Neuroscience 166:771–784

    Article  CAS  PubMed  Google Scholar 

  • Frosch D, Shoptaw S, Huber A, Rawson RA, Ling W (1996) Sexual HIV risk among gay and bisexual male methamphetamine abusers. J Subst Abuse Treat 13:483–486

    Article  CAS  PubMed  Google Scholar 

  • Graybiel AM, Rauch SL (2000) Toward a neurobiology of obsessive–compulsive disorder. Neuron 28:343–347

    Article  CAS  PubMed  Google Scholar 

  • Green AI, Halkitis PN (2006) Crystal methamphetamine and sexual sociality in an urban gay subculture: an elective affinity. Cult Health Sex 8:317–333

    Article  PubMed  Google Scholar 

  • Halkitis PN, Parsons JT, Stirratt MJ (2001) A double epidemic: crystal methamphetamine drug use in relation to HIV transmission among gay men. J Homosex 41:17–35

    Article  CAS  PubMed  Google Scholar 

  • Holder MK, Hadjimarkou MM, Zup SL, Blutstein T, Benham RS, McCarthy MM, Mong JA (2009) Methamphetamine facilitates female sexual behavior and enhances neuronal activation in the medial amygdala and ventromedial nucleus of the hypothalamus. Psychoneuroendocrinology 35:197–208

    Article  PubMed  Google Scholar 

  • Hull EM, Meisel RL, Sachs BD (2002) Male sexual behavior. In: Pfaff DW, Arnold AP, Etgen AM, Fahrbach SE, Rubin RT (eds) Hormones brain and behavior. Elsevier Science, San Diego, pp 1–138

    Google Scholar 

  • Jentsch JD, Taylor JR (1999) Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli. Psychopharmacology (Berl) 146:373–390

    Article  CAS  Google Scholar 

  • Kalechstein AD, Newton TF, Green M (2003) Methamphetamine dependence is associated with neurocognitive impairment in the initial phases of abstinence. J Neuropsychiatry Clin Neurosci 15:215–220

    CAS  PubMed  Google Scholar 

  • Kalivas PW, Volkow ND (2005) The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry 162:1403–1413

    Article  PubMed  Google Scholar 

  • Kalivas PW, Volkow N, Seamans J (2005) Unmanageable motivation in addiction: a pathology in prefrontal-accumbens glutamate transmission. Neuron 45:647–650

    Article  CAS  PubMed  Google Scholar 

  • Lawrence GJ, Kiefer SW (1987) Cessation of male rat copulatory behavior using illness as punishment: facilitation with a novel odor. Behav Neurosci 101:289–291

    Article  CAS  PubMed  Google Scholar 

  • London ED, Berman SM, Voytek B, Simon SL, Mandelkern MA, Monterosso J, Thompson PM, Brody AL, Geaga JA, Hong MS, Hayashi KM, Rawson RA, Ling W (2005) Cerebral metabolic dysfunction and impaired vigilance in recently abstinent methamphetamine abusers. Biol Psychiatry 58:770–778

    Article  CAS  PubMed  Google Scholar 

  • Marshall JF, Belcher AM, Feinstein EM, O’Dell SJ (2007) Methamphetamine-induced neural and cognitive changes in rodents. Addiction 102:61–69

    Article  PubMed  Google Scholar 

  • Martinez I, Paredes RG (2001) Only self-paced mating is rewarding in rats of both sexes. Horm Behav 40:510–517

    Article  CAS  PubMed  Google Scholar 

  • Mckirnan DJ, Vanable PA, Ostrow DG, Hope B (2001) Expectancies of sexual “escape” and sexual risk among drug and alcohol-involved gay and bisexual men. J Subst Abuse 13:137–154

    Article  CAS  PubMed  Google Scholar 

  • Melega WP, Williams AE, Schmitz DA, DiStefano EW, Cho AK (1995) Pharmacokinetic and pharmacodynamic analysis of the actions of d-amphetamine and d-methamphetamine on the dopamine terminal. J Pharmacol Exp Ther 274:90–96

    CAS  PubMed  Google Scholar 

  • NIDA (2006) Research report series: methamphetamine abuse and addiciton. NIH Publication Number 06-4210. Baltimore

  • Ornstein TJ, Iddon JL, Baldacchino AM, Sahakian BJ, London M, Everitt BJ, Robbins TW (2000) Profiles of cognitive dysfunction in chronic amphetamine and heroin abusers. Neuropharmacology 23:113–126

    CAS  Google Scholar 

  • Parsons JT, Halkitis PN (2002) Sexual and drug-using practices of HIV-positive men who frequent public and commercial sex environments. AIDS Care 14:815–826

    Article  CAS  PubMed  Google Scholar 

  • Paulus MP, Hozack N, Frank L, Brown GG, Schuckit MA (2003) Decision making by methamphetamine-dependent subjects is associated with error-rate-independent decrease in prefrontal and parietal activation. Biol Psychiatry 53:65–74

    Article  CAS  PubMed  Google Scholar 

  • Peters RH (1983) Learned aversions to copulatory behaviors in male rats. Behav Neurosci 97:140–145

    Article  CAS  PubMed  Google Scholar 

  • Peters RH, Blythe BL, Koch PC, Kueker CA (1989) Copulation–illness associations in male rats: lithium chloride dose and delay manipulations. Behav Neurosci 103:117–123

    Article  CAS  PubMed  Google Scholar 

  • Peugh J, Belenko S (2001) Alcohol, drugs and sexual function: a review. J Psychoactive Drugs 33:223–232

    CAS  PubMed  Google Scholar 

  • Pfaus JG (2009) Pathways of sexual desire. J Sex Med 6:1506–1533

    Article  CAS  PubMed  Google Scholar 

  • Pfaus JG, Pinel JPJ (1989) Alcohol inhibits and disinhibits sexual behavior in the male rat. Psychobiology 12:195–201

    Google Scholar 

  • Pfaus JG, Kippin TE, Centeno S (2001) Conditioning and sexual behavior: a review. Horm Behav 40:291–321

    Article  CAS  PubMed  Google Scholar 

  • Pinel JPJ, Pfaus JG, Christensen BK (1992) Contingent tolerance to the disruptive effects of alcohol on the copulatory behavior of male rats. Pharmacol Biochem Behav 41:133–137

    Article  CAS  PubMed  Google Scholar 

  • Pitchers KK, Balfour ME, Lehman MN, Richtand NM, Yu L, Coolen LM (2010) Neuroplasticity in the mesolimbic system induced by natural reward and subsequent reward abstinence. Biol Psychiatry 67:872–879

    Article  CAS  PubMed  Google Scholar 

  • Raj A, Saitz R, Cheng DM, Winter M, Samet JH (2007) Associations between alcohol, heroin, and cocaine use and high risk sexual behaviors among detoxification patients. Am J Drug Alcohol Abuse 33:169–178

    Article  PubMed  Google Scholar 

  • Rawson RA, Washton A, Domier CP, Reiber C (2002) Drugs and sexual effects: role of drug type and gender. J Subst Abuse Treat 22:103–108

    Article  PubMed  Google Scholar 

  • Reuter J, Raedler T, Rose M, Hand I, Glascher J, Buchel C (2005) Pathological gambling is linked to reduced activation of the mesolimbic reward system. Nat Neurosci 8:147–148

    Article  CAS  PubMed  Google Scholar 

  • Riviere GJ, Byrnes KA, Gentry WB, Owens SM (1999) Spontaneous locomotor activity and pharmacokinetics of intravenous methamphetamine and its metabolite amphetamine in the rat. J Pharmacol Exp Ther 291:1220–1226

    CAS  PubMed  Google Scholar 

  • Robbins TW, Everitt BJ (2002) Limbic–striatal memory systems and drug addiction. Neurobiol Learn Mem 78:625–636

    Article  CAS  PubMed  Google Scholar 

  • SAMHSA (2008) Results from the 2007 National Survey on Drug Use and Health: National Findings Substance Abuse and Mental Health Services Administration (SAMHSA), 2001. Office of Applied Studies, NHSDA Series H-13, Rockville

    Google Scholar 

  • Sánchez J, Comerford M, Chitwood DD, Fernandez MI, McCoy CB (2002) High risk sexual behaviours among heroin sniffers who have no history of injection drug use: implications for HIV risk reduction. AIDS Care 14:391–398

    Article  PubMed  Google Scholar 

  • Schilder AJ, Lampinen TM, Miller ML, Hogg RS (2005) Crystal methamphetamine and ecstasy differ in relation to unsafe sex among young gay men. Can J Public Health 96:340–343

    PubMed  Google Scholar 

  • Schröder N, O’Dell SJ, Marshall JF (2003) Neurotoxic methamphetamine regimen severely impairs recognition memory in rats. Synapse 49:89–96

    Article  PubMed  Google Scholar 

  • Semple SJ, Patterson TL, Grant I (2002) Motivations associated with methamphetamine use among HIV men who have sex with men. J Subst Abuse Treat 22:149–156

    Article  PubMed  Google Scholar 

  • Simon SL, Domier CP, Sim T, Richardson K, Rawson RA, Ling W (2001) Cognitive performance of current methamphetamine and cocaine abusers. J Addict Dis 21:61–74

    Article  Google Scholar 

  • Somlai AM, Kelly JA, McAuliffe TL, Ksobiech K, Hackl KL (2003) Predictors of HIV sexual risk behaviors in a community sample of injection drug-using men and women. AIDS Behav 7:383–393

    Article  PubMed  Google Scholar 

  • Springer A, Peters R, Shegog R, White D, Kelder S (2007) Methamphetamine use and sexual risk behaviors in U.S. high school students: findings from a national risk behavior survey. Prev Sci 8:103–113

    Article  PubMed  Google Scholar 

  • Taylor SF, Liberzon I, Decker LR, Koeppe RA (2002) A functional anatomic study of emotion in schizophrenia. Schizophr Res 58:159–172

    Article  PubMed  Google Scholar 

  • Tenk CM, Wilson H, Zhang Q, Pitchers KK, Coolen LM (2009) Sexual reward in male rats: effects of sexual experience on conditioned place preference associated with ejaculations and intromissions. Horm Behav 55:93–97

    Article  PubMed  Google Scholar 

  • Thompson PM, Hayashi KM, Simon SL, Geaga JA, Hong MS, Sui Y, Lee JY, Toga AW, Ling W, London ED (2004) Structural abnormalities in the brains of human subjects who use methamphetamine. J Neurosci 24:6028–6036

    Article  CAS  PubMed  Google Scholar 

  • Volkow ND, Chang L, Wang G-J, Fowler JS, Leonido-Yee M, Franceschi D, Sedler MJ, Gatley SJ, Hitzemann R, Ding Y-S, Logan J, Wong C, Miller EN (2001) Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. Am J Psychiatry 158:377–382

    Article  CAS  PubMed  Google Scholar 

  • Walsh SL, Wagner GC (1992) Motor impairments after methamphetamine-induced neurotoxicity in the rat. J Pharmacol Exp Ther 263:617–626

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported by grants from the National Institutes of Health R01 DA014591 and Canadian Institutes of Health Research RN 014705 to Lique M. Coolen.

Author information

Authors and Affiliations

  1. Department of Anatomy & Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, Medical Sciences Building, Room 460, London, ON, Canada, N6A 5C1

    Karla S. Frohmader, Michael N. Lehman & Lique M. Coolen

  2. Department of Physiology & Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada, N6A 5C1

    Katherine L. Bateman & Lique M. Coolen

Authors
  1. Karla S. Frohmader
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katherine L. Bateman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael N. Lehman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lique M. Coolen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lique M. Coolen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Frohmader, K.S., Bateman, K.L., Lehman, M.N. et al. Effects of methamphetamine on sexual performance and compulsive sex behavior in male rats. Psychopharmacology 212, 93–104 (2010). https://doi.org/10.1007/s00213-010-1930-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-010-1930-8

Keywords

Search

Navigation