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CB1 cannabinoid receptor activation dose dependently modulates neuronal activity within caudal but not rostral song control regions of adult zebra finch telencephalon

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Abstract

Rationale

CB1 cannabinoid receptors are distinctly expressed at high density within several regions of zebra finch telencephalon, including those known to be involved in song learning (lMAN and Area X) and production (HVC and RA) because (1) exposure to cannabinoid agonists during developmental periods of auditory and sensory-motor song learning alters song patterns produced later in adulthood and (2) densities of song region expression of CB1 waxes and wanes during song learning. It is becoming clear that CB1-receptor-mediated signaling is important to normal processes of vocal development.

Materials and methods

To better understand the mechanisms involved in cannabinoid modulation of vocal behavior, we have investigated the dose–response relationship between systemic cannabinoid exposure and changes in neuronal activity (as indicated by expression of the transcription factor, c-Fos) within telencephalic brain regions, with established involvement in song learning and/or control.

Results

In adults, we have found that low doses (0.1 mg/kg) of the cannabinoid agonist WIN-55212-2 decrease neuronal activity (as indicated by densities of c-fos-expressing nuclei) within vocal motor regions of caudal telencephalon (HVC and RA) while higher doses (3 mg/kg) stimulate activity. Both effects were reversed by pretreatment with the CB1-selective antagonist rimonabant. Interestingly, no effects of cannabinoid treatment were observed within the rostral song regions lMAN and Area X, despite distinct and dense CB1 receptor expression within these areas.

Conclusions

Overall, our results demonstrate that, depending on dosage, CB1 agonism can both inhibit and stimulate neuronal activity within brain regions controlling adult vocal motor output, implicating involvement of multiple CB1-sensitive neuronal circuits.

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Abbreviations

lMAN:

lateral magnocellular nucleus of the anterior nidopallium

Area X:

area X within songbird medial striatum

RA:

robust nucleus of the arcopallium

Uva:

nucleus uvaformis

DLM:

dorsal lateral nucleus of the medial thalamus

HVC:

used as a proper name (per Reiner et al. 2004a, b) to indicate a prominent vocal motor nucleus of zebra finch telencephalon

References

  • Bolhuis JJ, Hetebrij E, Den Boer-Visser AM, De Groot JH, Zijlstra GGO (2001) Localized immediate early gene expression related to the strength of song learning in socially reared zebra finches. Eur J Neurosci 13:2165–2170

    Article  PubMed  CAS  Google Scholar 

  • Bottjer SW, Johnson F (1997) Circuits, hormones, and learning: vocal behavior in songbirds. J Neurobiol 33:602–618

    Article  PubMed  CAS  Google Scholar 

  • Bottjer SW, Miesner EA, Arnold AP (1984) Forebrain lesions disrupt development but not maintenance of song in passerine birds. Science 224:901–903

    Article  PubMed  CAS  Google Scholar 

  • Chaperon F, Thiebot MH (1999) Behavioral effects of cannabinoid agents in animals. Crit Rev Neurobiol 13:243–281

    PubMed  CAS  Google Scholar 

  • Doupe AJ, Kuhl PK (1999) Bird song and human speech: common themes and mechanisms. Annu Rev Neurosci 22:567–631

    Article  PubMed  CAS  Google Scholar 

  • Elphick MR, Egertova M (2001) The neurobiology and evolution of cannabinoid signalling. Philos Trans R Soc Lond B Biol Sci 356:381–408

    Article  PubMed  CAS  Google Scholar 

  • Fowler CJ (2007) The pharmacology of the cannabinoid system—a question of efficacy and selectivity. Mol Neurobiol 36:15–25

    Article  PubMed  CAS  Google Scholar 

  • Mackie K, Hille B (1992) Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. Proc Natl Acad Sci USA 89:3825–3829

    Article  PubMed  CAS  Google Scholar 

  • Mackie K, Lai Y, Westenbroek R, Mitchell R (1995) Cannabinoids activate an inwardly rectifying potassium conductance and inhibit Q-type calcium currents in AtT20 cells transfected with rat brain cannabinoid receptor. J Neurosci 15:6552–6561

    PubMed  CAS  Google Scholar 

  • Mailleux P, Verslype M, Preud’homme X, Vanderhaeghen JJ (1994) Activation of multiple transcription factor genes by tetrahydrocannabinol in rat forebrain. Neuroreport 5:1265–1268

    PubMed  CAS  Google Scholar 

  • McGregor IS, Arnold JC, Weber MF, Topple AN, Hunt GE (1998) A comparison of delta 9-THC and anandamide induced c-fos expression in the rat forebrain. Brain Res 802:19–26

    Article  PubMed  CAS  Google Scholar 

  • Nottebohm F, Stokes TM, Leonard CM (1976) Central control of song in the canary, Serinus canarius. J Comp Neurol 165:457–486

    Article  PubMed  CAS  Google Scholar 

  • Patel S, Hillard CJ (2003) Cannabinoid-induced Fos expression within A10 dopaminergic neurons. Brain Res 963:15

    Article  PubMed  CAS  Google Scholar 

  • Patel NA, Moldow RL, Patel JA, Wu G, Chang SL (1998) Arachidonylethanolamide (AEA) activation of FOS proto-oncogene protein immunoreactivity in the rat brain. Brain Res 797:225–233

    Article  PubMed  CAS  Google Scholar 

  • Pertwee RG (1997) Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther 74:129–180

    Article  PubMed  CAS  Google Scholar 

  • Pertwee RG (2005) Inverse agonism and neutral antagonism at cannabinoid CB1 receptors. Life Sci 76:1307–1324

    Article  PubMed  CAS  Google Scholar 

  • Peterson RS, Yarram L, Schlinger BA, Saldanha CJ (2005) Aromatase is pre-synaptic and sexually dimorphic in the adult zebra finch brain. Proc Biol Sci 272:2089–2096

    Article  PubMed  CAS  Google Scholar 

  • Reiner A, Laverghetta AV, Meade CA, Cuthbertson SL, Bottjer SW (2004a) An immunohistochemical and pathway tracing study of the striatopallidal organization of area X in the male zebra finch. J Comp Neurol 469:239–261

    Article  PubMed  Google Scholar 

  • Reiner AP, Perkel DJ, Bruce L, Butler AB, Csillag A, Kunzel W, Medina L, Paxinos G, Shimizu T, Striedter G, Wild M, Ball GF, Durand S, Güntürkün O, Lee DW, Mello CV, Powers A, White SA, Hough G, Kubikova L, Smulders TV, Wada K, Dugas-Ford J, Husband S, Yamamoto K, Yu J, Siang C, Jarvis ED (2004b) Revised nomenclature for avian telencephalon and some related brainstem nuclei. J Comp Neurol 473:377–414

    Article  PubMed  Google Scholar 

  • Reiner A, Yamamoto K, Karten HJ (2005) Organization and evolution of the avian forebrain. Anat Rec A Discov Mol Cell Evol Biol 287A:1080–1102

    Article  Google Scholar 

  • Scharff C, Nottebohm F (1991) A comparative study of the behavioral deficits following lesions of various parts of the zebra finch song system: implications for vocal learning. J Neurosci 11(9):2896–2913

    PubMed  CAS  Google Scholar 

  • Soderstrom K, Johnson F (2001) The zebra finch CB1 cannabinoid receptor: pharmacology and in vivo and in vitro effects of activation. J Pharmacol Exp Ther 297:189–197

    PubMed  CAS  Google Scholar 

  • Soderstrom K, Johnson F (2003) Cannabinoid exposure alters learning of zebra finch vocal patterns. Brain Res Dev Brain Res 142:215–217

    Article  PubMed  CAS  Google Scholar 

  • Soderstrom K, Tian Q (2004) Distinct periods of cannabinoid sensitivity during zebra finch vocal development. Dev Brain Res 153:225–232

    Article  CAS  Google Scholar 

  • Soderstrom K, Tian Q (2006) Developmental pattern of CB1 cannabinoid receptor immunoreactivity in brain regions important to zebra finch (Taeniopygia guttata) song learning and control. J Comp Neurol 496:739–758

    Article  PubMed  Google Scholar 

  • Soderstrom K, Leid M, Moore FL, Murray TF (2000) Behavioral, pharmacological and molecular characterization of an amphibian cannabinoid receptor. J Neurochem 75:413–423

    Article  PubMed  CAS  Google Scholar 

  • Soderstrom K, Tian Q, Valenti M, Di Marzo V (2004) Endocannabinoids link feeding state and auditory perception-related gene expression. J Neurosci 24:10013–10021

    Article  PubMed  CAS  Google Scholar 

  • Soderstrom K, Qin W, Leggett MH (2007) A minimally invasive procedure for sexing young zebra finches. J Neurosci Methods 164:116–119

    Article  PubMed  Google Scholar 

  • Spear L (2000) Modeling adolescent development and alcohol use in animals. Alcohol Res Health 24:115–123

    PubMed  CAS  Google Scholar 

  • Troyer TW, Bottjer SW (2001) Bird song: models and mechanisms. Curr Opin Neurobiol 11(6):721–726

    Article  PubMed  CAS  Google Scholar 

  • Whitney O, Soderstrom K, Johnson F (2003) CB1 cannabinoid receptor activation inhibits a neural correlate of song recognition in an auditory/perceptual region of the zebra finch telencephalon. J Neurobiol 56:266–274

    Article  PubMed  CAS  Google Scholar 

  • Wilson RI, Nicoll RA (2002) Endocannabinoid signaling in the brain. Science 296:678–682

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

We are grateful to Bin Luo who managed the breeding aviary and assisted in these experiments.

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Correspondence to Ken Soderstrom.

Additional information

This work was supported by NIDA grants R01DA020109 and R21DA14693.

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Soderstrom, K., Tian, Q. CB1 cannabinoid receptor activation dose dependently modulates neuronal activity within caudal but not rostral song control regions of adult zebra finch telencephalon. Psychopharmacology 199, 265–273 (2008). https://doi.org/10.1007/s00213-008-1190-z

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  • DOI: https://doi.org/10.1007/s00213-008-1190-z

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