Summary
Behavioral effect of galanin and its fragments, galanin1–15 and galanin16–29 (200 ng, 1 and 5 μg), after intracerebroventricular (i.c.v.) administration was studied in rats. The number of crossings and pippings and the time of locomotion (an open field test) showed a similar sedative action of galanin and galanin16–29, with no significant effect of galanin1–15. Galanin and its fragments, injected in doses of 200 ng, 1 and 5 μg, did not affect nociception, as measured by a tail-flick and paw pressure test. Galanin and galanin1–15, but not galanin16–29 (5 μg i.c.v.), injected together with morphine (2.5 μg i.c.v.), significantly potentiated the analgetic effect of morphine assessed by a paw pressure test; a similar tendency was also observed in a tail-flick test. Galanin and its two fragments injected in doses of 200 ng, 1 and 5 μg, did not change the effect of morphine given in a dose of 1 μg. These data suggest that galanin, having no effect when given alone, potentiate the analgetic effect of morphine. The fact that the N-terminal fragment of galanin acts like a natural peptide suggests a receptor mediated action.
In conclusion, the analgesic effect of morphine was potentiated by galanin and its N-terminal fragment galanin1–15. On the other hand, behavioral study showed a similar sedative action of galanin and C-terminal fragment galanin16–29. This suggests that the N- and C-terminal fragments of galanin are differentially involved in behavioral effects of the peptide.
Similar content being viewed by others
References
Bartfai T, Fisone G, Langel Ü (1992) Galanin and galanin antagonists: molecular and biochemical perspectives. TIPS 13: 312–317
Bartfai T, Langel U, Bedecs K, Andell S, Land T, Gregersen S, Ahren B, Girotti P, Consolo S, Corwin R (1993) Galanin-receptor ligand M40 peptide distinguishes between putative-receptor subtypes. Proc Natl Acad Sci USA 90(23): 11287–11291
Ch'ng JLC, Christofides ND, Anand P, Gibson SJ, Allen YS, Su HC, Tatemoto K, Morrison JFB, Polak JM, Bloom SR (1985) Distribution of galanin immunoreactivity in the central nervous system and the responses of galanin-containing neuronal pathways to injury. Neuroscience 16, 2: 343–354
Fisone G, Berthold M, Bedecs K, Undën A, Bartfai T, Bertorelli R, Consolo S, Crawley J, Martin B, Nilsson S, Hökfelt T (1989) N-terminal galanin-(1–16) fragment is an agonist at the hippocampal galanin receptor. Proc Natl Acad Sci USA 86: 9588–9591
Hökfelt T, Wiesenfeld-Hallin Z, Villar M, Melander T (1989) Increase of galanin-like immunoreactivity in rat dorsal root ganglion cells after peripheral axotomy. Neurosci Lett 83: 217–220
Katsoulis S, Schmidt WE, Schworer H, Creutzfeldt W (1990) Effects of galanin, its analogues and fragments on rat isolated fundus strips. Br J Pharmacol 101: 297–300
Mungan Z, Ozmen V, Ertan A, Coy DH, Baylor LM, Rice JC, Rossowski WJ (1992) Structural requirements for galanin inhibition of pentagastrin-stimulated gastric acid secretion in conscious rats. Eur J Pharmacol 214: 53–57
Papka RE, McNeill L (1992) Coexistence of calcitonin gene-related peptide and galanin immunoractivity in female rat pelvic and lumbosacral dorsal root ganglia. Peptides 13: 761–767
Post C, Alari L, Hökfelt T (1990) Intrathecal galanin increases the latency in the tail-flick and hot-plate tests in mouse. Acta Physiol Scand 132: 583–584
Rossowski WJ, Rossowski TM, Zacharia S, Ertan A, Coy DH (1990) Galanin binding sites in rat gastric and jejunal smooth muscle membrane preparations. Peptides 11(2): 333–338
Sundström E, Melander T (1988) Effects of galanin on 5-HT neurons in the rat CNS. Eur J Pharmacol 146: 327–329
Villar MJ, Cortës R, Theodorsson E, Wiesenfeld-Hallin Z, Schalling M, Fahrenkrug J, Emson PC, Hökfelt T (1989) Neuropeptide expression in rat dorsal root ganglion cells and spinal cord after peripheral nerve injury with special reference to galanin. Neuroscience 33, 3: 587–604
Wiesenfeld-Hallin Z, Villar MJ, Hökfelt T (1988) Intrathecal galanin at low doses increases spinal reflex excitability in rats more to thermal than mechanical stimuli. Exp Brain Res 71: 663–666
Wiesenfeld-Hallin Z, Villar MJ, Hökfelt T (1989a) The effects of intrathecal galanin and C-fiber stimulation on the flexor reflex in the rat. Brain Res 486: 205–213
Wiesenfeld-Hallin Z, Xu X-J, Villar M, Hökfelt T (1989b) The effect of intrathecal galanin on the flexor reflex in rat: increased depression after sciatic nerve section. Neurosci Lett 105: 149–154
Wiesenfeld-Hallin Z, Xu X-J, Villar MJ, Hökfelt T (1990) Intrathecal galanin potentiates the spinal cord analgesic effect of morphine: electrophysiological and behavioral studies. Neurosci Lett 109: 217–221
Xu X-J, Wiesenfeld-Hallin Z, Villar MJ, Hökfelt T (1989) Intrathecal galanin antagonizes the facilitatory effect of substance P on the nociceptive flexor reflex in the rat. Acta Physiol Scand 137: 463–464
Xu X-J, Wiesenfeld-Hallin Z, Fisone G, Bartfai T, Hökfelt T (1990) The N-terminal 1–16, but not C-terminal 17–29, galanin fragment affects the flexor reflex in rats. Eur J Pharmacol 182: 137–141
Xu X-J, Wiesenfeld-Hallin Z, Hökfelt T (1991) Intrathecal galanin blocks the prolonged increase in spinal cord flexor reflex excitability induced by conditioning stimulation of unmyelinated muscle afferents in the rat. Brain Res 541: 359–353
Yaksh TL, DuChateau JC, Rudy TA (1976) Antagonism by methysergide and cinanserin of the antiniciceptive action of morphine administered into the periaqueductal gray. Brain Res 104: 367–372
Yaksh TL, Plant RI, Rudy TA (1977) Studies on the antagonism by raphe lesions of the antinociceptive action of systemic morphine. Eur J Pharmacol 41: 399–408
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Przewłocka, B., Machelska, H., Rekowski, P. et al. Intracerebroventricular galanin and N-terminal galanin fragment enhance the morphine-induced analgesia in the rat. J. Neural Transmission 102, 229–235 (1995). https://doi.org/10.1007/BF01281157
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01281157