Abstract
The effects of GABA agonists and antagonists on penile erection (PE) induced by apomorphine were investigated in rats. Subcutaneous (SC) administration of apomorphine (0.01–0.1 mg/kg) induces a dose-dependent PE in rats. The maximum effect was obtained with 0.1 mg/kg of the drug. The response was decreased with increasing doses of apomorphine from 0.1 to 0.5 mg/kg. The response induced by apomorphine (0.1–0.5 mg/kg) was decreased in animals pretreated with either the GABA-A agonist muscimol or the GABA-B agonist baclofen. Combination of muscimol with baclofen caused a stronger inhibitory effect on apomorphine-induced PE. Bicuculline or picrotoxin but not phaclofen reduced the inhibitory effect of muscimol on PE induced by apomorphine, whereas phaclofen but not GABA-A antagonists decreased the inhibitory action of baclofen on apomorphine-induced PE. Pretreatment of animals with higher doses of the GABA-A antagonists bicuculline and picrotoxin or the GABA-B antagonist phaclofen elicited inhibition of apomorphine-induced PE. However, the inhibitory effects of GABA-A and GABA-B antagonists are lost on combination. Administration of GABA-A and GABA-B receptor stimulation inhibit PE induced by dopaminergic mechanism(s).
Similar content being viewed by others
References
Agmo A, Paredes R (1985) GABAergic drugs and sexual behaviour in the male rat. Eur J Pharmacol 112:371–378
Bartholini G (1980) Interaction of striatal dopaminergic, cholinergic and GABA-ergic neurons: relation to extrapyramidal function. Trends Pharmacol Sci 1:138–140
Benassi-Benelli A, Ferari F, Pellegrini P, Quarantotti B (1979) Penile erection induced by apomorphine andN-n-propyl-norapomorphine in rats. Arch Int Pharmacodyn 242:241–247
Berendsen HHG, Broekkamp CLE (1987) Drug-induced penile erections in rats: indications of serotonin-1B receptor mediation. Eur J Pharmacol 135:279–287
Bitran D, Miller SA, McQuade DB, Leipheimer RE, Sachs BD (1989) Inhibition of sexual reflexes by lumbosacral injection of a GABA-B agonist in the male rat. Pharmacol Biochem Behav 31:657–666
Blume HW, Pittman QJ, Renaud LP (1981) Sensitivity of identified medial hypothalamic neurons to GABA, glycine and related amino acids: influence of bicuculline, picrotoxin and strymidine on synaptic inhibition. Brain Res 205: 145
Bonanno G, Cavazzani P, Andrioli GC, Asaro AD, Pellegrini G, Raiteri M (1989) Release-regulating autoreceptors of the GABA-B type in human cerebral cortex. Br J Pharmacol 96:341–346
Bowery NG, Hill DR, Hudson AL, Doble A, Middlemiss DN, Shaw J, Turnbull MJ (1980) (—)-Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor. Nature 283:92–94
Bowery NG, Doble A, Hill DR, Hudson AL, Shaw JS, Turnbull MJ, Warrington R (1981) Bicuculline-insensitive GABA receptors on peripheral autonomic nerve terminals. Eur J Pharmacol 71:53–70
Bowery NG, Hill DR, Hudson AL (1983) Characteristics of GABA-B receptor binding sites on rat whole brain synaptic membranes. Br J Pharmacol 78:191–206
Bowery NG, Price GW, Hudson AL, Hill DR, Wilkin GP, Turnbull MJ (1984) GABA receptor multipilicity: visualization of different receptor types in the mammalian CNS. Neuropharmacology 23:219–231
Cheramy A, Nieouillon A, Glowinski J (1978) GABA-ergic processes involved in the control of dopamine release from nigrostriatal dopaminergic neurons in the cat. Eur J Pharmacol 48:281–295
Creese I, Sibley DR, Hamblin MW, Leff SE (1983) The classification of dopamine receptors: relationship to radioligand binding. Annu Rev Neurosci 6:43–71
Defeudis FV (1977) GABA-receptors in the vertebrate nervous system. Prog Neurobiol 9:123–145
Fernandez-Guasti A, Larsson K, Beyer C (1986) GABAergic control of masculine sexual behaviour. Pharmacol Biochem Behav 24:1065–1070
Forchetti CM, Meek JL (1981) Evidence for a tonic GABAergic control of serotonin neurons in the median raphe nucleus. Brain Res 206:208–212
Gale K, Casu M (1981) Dynamic utilization of GABA in substantianigra: regulation by dopamine and GABA in the striatum, and its clinical and behavioural implications. Mol Cell Biochem 39:369–405
Girault JA, Spampinato U, Glowinski J, Besson MJ (1986) In vivo release of [3H] gamma-aminobutyric acid in the rat neostriatum-II. opposing effects of D1 and D2 dopamine receptor stimulation in the dorsal caudate putamen. Neuroscience 19:1109–1117
Gower AJ, Berendsen HHG, Princen MM, Broekkamp CLE (1984) The yawning-penile erection syndrome as a model for putative dopamine autoreceptor activity. Eur J Pharmacol 103:81–87
Gower AJ, Berendsen HHG, Broekkamp CLE (1986) Antagonism of drug-induced yawning and penile erections in rats. Eur J Pharmacol 122:239–244
Hill DR, Bowery NG (1981)3H-baclofen and3H-GABA bind to bicuculline-insensitive GABA-B sites in rat brain. Nature 290:149–152
Hull EM, Eaton RC, Markowski VP, Moses J, Lumley LA, Loucks JA (1992) Opposite influence of medial preoptic D1 and D2 receptors on genital reflexes: implications for copulation. Life Sci 51:1705–1713
Johnston GAR (1978) Neuropharmacology of amino acid inhibitory transmitters. Annu Rev Pharmacol Toxicol 18:269–289
Jones DL, Mogenson GJ (1980) Nucleus accumbens to globus pallidus GABA projection: electrophysiological and iontophorectic investigations, Brain Res 188:93–105
Kerr DIB, Ong J, Prager RH, Gynther BD, Curtis DR (1987) Phaclofen: a peripheral and central baclofen antagonist. Brain Res 405:150–154
Leipheimer RE, Sachs BD (1988) GABAergic regulation of penile reflexes and copulation in rats. Physiol Behav 42:351–357
Mitchell PR, Martin IL (1978) Is GABA release modulated by presynaptic receptors? Nature 274:904–905
Nishikawa T, Scatton B (1983) Evidence for a GABAergic inhibitory influence on serotonergic neurons originating from the dorsal raphe. Brain Res 279:325–329
Pacitti C, Fiadone G, Gasbarri A, Civitelli D, Scarnati E (1982) Electrophysiological evidence for an inhibitory accumbens-entopeduncular pathway in the rat. Neurosci Lett 33:35–40
Pehek EA, Thompson JT, Eaton RC, Bazzett TJ, Hull EM (1988) Apomorphine and haloperidol, but not domperidone, affect penile reflexes in rats. Pharmacol Biochem Behav 31:201–208
Pehek EA, Thompson JT, Hull EM (1989) The effects of intracranial administration of the dopamine agonist apomorphine on penile reflexes and seminal emission in the rat. Brain Res 500:325–332
Reimann W, Zumstein A, Starke K (1982) γ-Aminobutyric acid can both inhibit and facilitate dopamine release in the caudate nucleus of the rabbit. J Neurochem 39:961–969
Seeman P (1980) Brain dopamine receptors. Pharmacol Rev 32:229–313
Serra G, Collu M, Loddo A, Celasco G, Gessa GL (1983) Hypophysectomy prevents yawning and penile erection but not hypomotility induced by apomorphine. Pharmacol Biochem Behav 19:917–919
Stoof JC, Kebabian JW (1984) Two dopamine receptors: biochemistry, physiology, pharmacology. Life Sci 35:2281–2296
Ticku MK, Maksay G (1983) Convulsant/depressant site of action at the allosteric benzodiazepine-GABA receptor-ionophore complex. Life Sci 33:2363–2375
Walaas I, Fonnum F (1980) Biochemical evidence for γ-aminobutyrate containing fibers from the nucleus accumbens to the substantia-nigra and ventral tegmental area in the rat. Neuroscience 5:63–72
Wood PL (1980) Actions of GABA-ergic agents on dopamine metabolism in the nigrostriatal pathway of the rat. J Pharmacol Exp Ther 222:674–679
Zarrindast MR, Shokravi S, Samini M (1992) Opposite influences of dopaminergic receptor subtypes on penile erection. Gen Pharmacol 23:671–675
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zarrindast, MR., Farahvash, H. Effects of GABA-ergic drugs on penile erection induced by apomorphine in rats. Psychopharmacology 115, 249–253 (1994). https://doi.org/10.1007/BF02244779
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02244779