Skip to main content
SpringerLink
Log in

Low anandamide doses facilitate male rat sexual behaviour through the activation of CB1 receptors

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

Abstract

Rationale

Endocannabinoids (eCN) exert biphasic effects on several behaviours; however, they have only been reported to inhibit male sexual behaviour. eCN, the endogenous ligands for CB1 receptors, are released in response to neuronal stimulation and regulate the functioning of the mesocorticolimbic system (MCL), which is activated by male sexual behaviour. We hypothesised that eCN might exert biphasic effects on male rat copulatory behaviour and be released during copulation to satiation as a result of the repeated activation of the MCL system.

Objectives

The study was conducted to determine if the eCN anandamide exerts biphasic effects on sexual behaviour expression of sexually experienced and sexually satiated male rats and to establish the possible participation of eCN in the sexual satiation phenomenon.

Methods

The eCN anandamide and the CB1 receptor antagonist AM251 were systemically administered to sexually experienced or sexually satiated rats and their effects on copulatory behaviour analysed.

Results

Low anandamide doses facilitated sexual behaviour expression in sexually experienced and in sexually satiated rats by acting at CB1 receptors. AM251 blocked the establishment of the sexual inhibition that characterises sexual satiation, but did not reverse it once established.

Conclusions

Anandamide exerts dose-based biphasic effects on copulatory behaviour of sexually experienced male rats and facilitates sexual behaviour expression of sexually satiated animals at low doses. eCN participate in the establishment, but not in the maintenance of the sexual inhibitory state that characterises the sexual satiation phenomenon.

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
Fig. 5

Similar content being viewed by others

References

  • Alger BE, Kim J (2011) Supply and demand for endocannabinoids. Trends Neurosci 34:304–315

    Google Scholar 

  • Balfour M, Yu L, Coolen L (2004) Sexual behavior and sex-associated environmental cues activate the mesolimbic system in male rats. Neuropsychopharmacology 29:718–730

    Article  PubMed  CAS  Google Scholar 

  • Beach F, Jordan L (1956) Sexual exhaustion and recovery in the male rat. Q J Exp Psychol 8:121–133

    Article  Google Scholar 

  • Berridge KC (2007) The debate over dopamine’s role in reward: the case for incentive salience. Psychopharmacology 191:391–431

    Article  PubMed  CAS  Google Scholar 

  • Canseco-Alba A, Rodríguez-Manzo G (2013) Anandamide transforms non copulating rats into sexually active animals. J Sex Med 10:686–693

    Article  PubMed  CAS  Google Scholar 

  • Damsma G, Pfaus JG, Wenkstern D, Phillips AG, Fibiger HC (1992) Sexual behavior increases dopamine transmission in the nucleus accumbens and striatum of male rats: comparison with novelty and locomotion. Behav Neurosci 106:181–191

    Article  PubMed  CAS  Google Scholar 

  • Di Marzo V, Melck D, Bisogno T, De Petrocellis L (1998) Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action. Trends Neurosci 21:521–528

    Article  PubMed  Google Scholar 

  • Ferrari F, Ottani D, Giuliani D (2000) Inhibitory effects of the cannabinoid agonist HU 210 on rat sexual behavior. Physiol Behav 69:547–554

    Article  PubMed  CAS  Google Scholar 

  • Fiorino DF, Coury A, Phillips AG (1997) Dynamic changes in nucleus accumbens dopamine efflux during the Coolidge effect in male rats. J Neurosci 17:4849–4855

    PubMed  CAS  Google Scholar 

  • Fride E, Mechoulam R (1993) Pharmacological activity of the cannabinoid receptor agonist, anandamide, a brain constituent. Eur J Pharmacol 231:313–314

    Article  PubMed  CAS  Google Scholar 

  • Gardner E (2005) Endocannabinoid signaling system and brain reward: emphasis on dopamine. Pharmacol Biochem Behav 81:263–284

    Article  PubMed  CAS  Google Scholar 

  • Garduño-Gutiérrez R, Guadarrama-Bazante L, León-Olea M, Rodríguez-Manzo G (2013) Endogenous opioids mediate the sexual inhibition, but not the drug hypersensitivity induced by sexual satiation in male rats. Behav Neurosci 127:458–464

    Article  PubMed  Google Scholar 

  • Gorzalka B, Morrish A, Hill G (2008) Endocannabinoid modulation of male rat sexual behavior. Psychopharmacology (Berl) 198:479–486

    Article  CAS  Google Scholar 

  • Hernández-González M, Guevara MA, Morali G, Cervantes M (1997) Subcortical multiple unit activity changes during rat male sexual behavior. Physiol Behav 61:285–291

    Article  PubMed  Google Scholar 

  • Johnson SW, North RA (1992) Opioids excite dopamine neurons by hyperpolarization of local interneurons. J Neurosci 12:483–488

    PubMed  CAS  Google Scholar 

  • Kelley A, Berridge K (2002) The neuroscience of natural rewards: relevance to addictive drugs. J Neurosci 22:3306–3311

    PubMed  CAS  Google Scholar 

  • Larsson K (1956) Conditioning and sexual behaviour in the male albino rat. Almqvist and Wiksell, Stockholm

    Google Scholar 

  • Lobb CJ, Troyer TW, Wilson CJ, Paladini CA (2011) Disinhibition bursting of dopaminergic neurons. Front Syst Neurosci 5:1–8

    Article  Google Scholar 

  • Lupica C, Riegel A, Hoffman A (2004) Marijuana and cannabinoid regulation of brain reward circuits. Br J Pharmacol 143:227–234

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Martínez-González D, Bonilla-Jaime H, Morales-Otal A, Henriksen SJ, Velázquez-Moctezuma J, Prospéro-García O (2004) Oleamide and anandamide effects on food intake and sexual behavior of rats. Neurosci Lett 364:1–6

    Article  PubMed  Google Scholar 

  • Mas M, Gonzales-Mora JL, Louilot A, Solé C, Guadalupe T (1990) Increased dopamine release in the nucleus accumbens of copulating male rats as evidenced by in vivo voltammetry. Neurosci Lett 110:303–308

    Google Scholar 

  • Merari A, Barak A, Plaves M (1973) Effects of 1(2)-tetrahydrocannabinol on copulation in the male rat. Psychopharmacologia 28:243–246

    Article  PubMed  CAS  Google Scholar 

  • Micale V, Cristino L, Tamburella A, Petrosino S, Leggio GM, Drago F, Di Marzo V (2009) Anxiolytic effects in mice of a dual blocker of fatty acid amide hydrolase and transient receptor potential vanilloid type-1 channels. Neuropsychopharmacology 34:593–606

    Article  PubMed  CAS  Google Scholar 

  • Murphy LL, Gher J, Steger RW, Bartke A (1994) Effects of delta9-tetrahydrocannabinol on copulatory behavior and neuroendocrine responses of male rats to female conspecifics. Pharmacol Biochem Behav 48:1011–1017

    Google Scholar 

  • Pfaus JG, Damsma G, Wenkstern DG, Blaha CD, Phillips AG, Fibiger HC (1990) Sexual behavior enhances central dopamine transmission in the rat. Brain Res 530:345–348

    Article  PubMed  CAS  Google Scholar 

  • Pleim ET, Matochik JA, Barfield RJ, Auerbach SB (1990) Correlation of dopamine release in the nucleus accumbens with masculine sexual behavior in rats. Brain Res 524:160–163

    Article  PubMed  CAS  Google Scholar 

  • Rodríguez-Manzo G, Fernández-Guasti A (1994) Reversal of sexual exhaustion by serotonergic and noradrenergic agents. Behav Brain Res 62:127–134

    Article  PubMed  Google Scholar 

  • Rodríguez-Manzo G, Guadarrama-Bazante IL, Morales-Calderón A (2011) Recovery from sexual exhaustion-induced copulatory inhibition and drug hypersensitivity follow a same time course: two expressions of a same process? Behav Brain Res 217:253–260

    Article  PubMed  Google Scholar 

  • Ross RA (2003) Anandamide and vanilloid TRPV1 receptors. Br J Pharmacol 140:790–801

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Rubino T, Realini N, Castiglioni C, Guidali C, Vigano D, Marras E, Petrosino S, Perletti G, Maccarrone M, Di Marzo V, Parolaro D (2008) Role in anxiety behavior of the endocannabinoid system in the prefrontal cortex. Cereb Cortex 18:1292–1301

    Article  PubMed  CAS  Google Scholar 

  • Scherma M, Medalie J, Fratta W, Vadivel SK, Makriyannis A, Piomelli D, Mikics E, Haller J, Yasar S, Tanda G, Goldberg SR (2008) The endogenous cannabinoid anandamide has effects on motivation and anxiety that are revealed by fatty acid amide hydrolase (FAAH) inhibition. Neuropharmacology 54:129–140

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Stewart J (1995) How does incentive motivational theory apply to sexual behaviour? In: Bancroft J (ed) The pharmacology of sexual function and dysfunction. Elsevier Science, Amsterdam

    Google Scholar 

  • Sulcova E, Mechoulam R, Fride E (1998) Biphasic effects of anandamide. Pharmacol Biochem Behav 59:347–352

    Article  PubMed  CAS  Google Scholar 

  • Swanson LW (1982) The projections of the ventral tegmental area and adjacent regions: a combined fluorescent retrograde tracer and immunofluorescence study in the rat. Brain Res Bull 9:321–353

    Article  PubMed  CAS  Google Scholar 

  • Szabo B, Siemes S, Wallmichrath I (2002) Inhibition of GABAergic neurotransmission in the ventral tegmental area by cannabinoids. Eur J Neurosci 15:2057–2061

    Article  PubMed  Google Scholar 

  • Umathe SN, Manna SS, Jain NS (2012) Endocannabinoid analogues exacerbate marble-burying behavior in mice via TRPV1 receptor. Neuropharmacology 62:2024–2033

    Article  PubMed  CAS  Google Scholar 

  • Wenkstern D, Pfaus JG, Fibiger HC (1993) Dopamine transmission increases in the nucleus accumbens of male rats during first exposure to sexually receptive female rats. Brain Res 618:41–46

    Article  PubMed  CAS  Google Scholar 

  • Wu X, French ED (2000) Effects of chronic delta-9-tetrahydrocannabinol on rat midbrain dopamine neurons: an electrophysiological assessment. Neuropharmacology 39:391–398

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Authors wish to thank Miss Ángeles Ceja Gálvez for animal care. The data here reported are part of the MSc dissertation of Ana Canseco-Alba who received a scholarship from Conacyt (Nr. 232728)

Author information

Authors and Affiliations

  1. Departamento de Farmacobiología, Cinvestav-Sede Sur, Calzada de los Tenorios 235, Col. Granjas Coapa, Delegación Tlalpan, 14330, México D.F, México

    Ana Canseco-Alba & Gabriela Rodríguez-Manzo

Authors
  1. Ana Canseco-Alba
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gabriela Rodríguez-Manzo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gabriela Rodríguez-Manzo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Canseco-Alba, A., Rodríguez-Manzo, G. Low anandamide doses facilitate male rat sexual behaviour through the activation of CB1 receptors. Psychopharmacology 231, 4071–4080 (2014). https://doi.org/10.1007/s00213-014-3547-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-014-3547-9

Keywords

Search

Navigation