, Volume 86, Issue 1–2, pp 31–36

Cocaine: Excitatory effects on sensorimotor reactivity measured with acoustic startle

  • Michael Davis
Original Investigations


Cocaine (2.5–10 mg/kg) caused a dose-related increase in the amplitude of the acoustic startle reflex in rats. In contrast, procaine (5–40 mg/kg) caused a dose-related decrease in startle, indicating that the effects of cocaine could not be ascribed to its local anesthetic effects. Cocaine's excitatory effects were blocked by pretreatment with haloperidol (0.5 mg/kg) but not by cyproheptadine or prazosin. The excitatory effects of cocaine (10 mg/kg) were markedly attenuated by pretreatment with reserpine (5 mg/kg 24 and 18 h earlier) but not by α-methyl-p-tyrosine (100 mg/kg 1 h earlier). In contrast, comparably sized excitatory effects of d-amphetamine were blocked by α-methyl-p-tyrosine and greatly enhanced by pretreatment with reserpine. Neither pretreatment blocked excitatory effects of apomorphine on startle. The data indicate that cocaine increases startle by acting through reserpine-sensitive pools of dopamine and provide further support for the conclusion that acoustic startle is enhanced by activation of dopamine receptors.

Key words

Cocaine Startle Acoustic startle Amphetamine Apomorphine Stimulants 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Astrachan DI, Davis M (1981) Spinal modulation of the acoustic startle response: The role of norepinephrine, serotonin and dopamine. Brain Res 206:223–228Google Scholar
  2. Astrachan DI, Davis M, Gallager DW (1983) Behavior and binding: Correlations between α1-adrenoceptor stimulation of acoustic startle and α1-adrenoceptor occupancy and number in rat lumbar spinal cord. Brain Res 260:81–90Google Scholar
  3. Chikamori Y, Sasa M, Fujimoto S, Takori S, Matsuoka I (1980) Locus coeruleus-induced inhibition of dorsal cochlear nucleus neurons in comparison with lateral vestibular nucleus neurons. Brain Res 194:53–63Google Scholar
  4. Chiueh CC, Moore KE (1975) Blockade by reserpine of methylphenidate-induced release of brain dopamine. J Pharmacol Exp Ther 193:559–563Google Scholar
  5. Colpaert FC, Niemegeers JE, Janssen PAJ (1978) Neuroleptic interference with cocaine cue: Internal stimulus control of behavior and psychosis. Psychopharmacology 58:347–367Google Scholar
  6. Creese I, Iversen SD (1975) The pharmacological and anatomical substrates of the amphetamine response in the rat. Brain Res 83:419–436Google Scholar
  7. Davis M (1980) Neurochemical modulation of sensory-motor reactivity: acoustic and tactile startle reflexes. Neurosci Biobehav Rev 4:241–263Google Scholar
  8. Davis M, Aghajanian GK (1976) Effects of apomorphine and haloperidol on the acoustic startle response in rats. Psychopharmacology 47:217–223Google Scholar
  9. Davis M, Svensson TH, Aghajanian GK (1975) Effects of d- and l-amphetamine on habituation and sensitization of the acoustic startle response in rats. Psychopharmacology 43:1–11Google Scholar
  10. Davis M, Astrachan DI, Gendelman PM, Gendelman DS (1980) 5-Methoxy-N,N-dimethyl-tryptamine: Spinal cord and brainstem mediation of excitatory effects on acoustic startle. Psychopharmacology 70:123–130Google Scholar
  11. Davis M, Kehne JH, Commissaris RL (1985) Antagonism of apomorphine-enhanced startle by α1-adrenergic antagonists. Eur J Pharmacol 108:233–241Google Scholar
  12. Ford RD, Balster RL (1977) Reinforcing properties of intravenous procaine in rhesus monkeys. Pharmacol Biochem Behav 6:289–296Google Scholar
  13. Geyer MA, Peterson LR, Rose GJ, Horwitt DD, Light RR, Adams LM, Zook JA, Hawkins RL, Mandell AJ (1978) The effects of LSD and mescaline-derived hallucinogens on sensory integrative function: Tactile startle. J Pharmacol Exp Ther 207:837–847Google Scholar
  14. Hadfield MG, Nugent EA (1983) Cocaine: Comparative effect on dopamine uptake in extrapyramidal and limbic systems. Biochem Pharmacol 32:744–746Google Scholar
  15. Heikkila RE, Cabbat FS, Manzino L, Duvoisin RC (1979) Rotational behavior induced by cocaine analogs in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra: Dependence upon dopamine uptake inhibition. J Pharmacol Exp Ther 211:189–194Google Scholar
  16. Herling S, Woods JH (1980) Chlorpromazine effects on cocaine-reinforced responding in rhesus monkeys: Reciprocal modification of rate-altering effects of the drugs. J Pharmacol Exp Ther 214:354–361Google Scholar
  17. Hertting G, Axelford J, Whitby LG (1961) Effect of drugs on the uptake and metabolism of 3H-norepinephrine. J Pharmacol Exp Ther 134:146–153Google Scholar
  18. Huang D, Wilson MC (1984) The effects of dl-cathinone, d-amphetamine and cocaine on avoidance responding in rats and their interactions with haloperidol and methysergide. Pharmacol Biochem Behav 20:721–729Google Scholar
  19. Kehne JH, Sorenson CA (1978) The effects of pimozide and phenoxybenzamine pretreatments on amphetamine and apomorphine potentiation of the acoustic startle response in rats. Psychopharmacology 58:137–142Google Scholar
  20. Kirkby RJ, Bell DS, Preston AC (1972) The effects of methylamphetamine on stereotyped behavior, activity, startle and orienting response. Psychopharmacology 25:41–48Google Scholar
  21. Kobinger W (1958) Differentiation between the sedative actions of 5-hydroxytryptamine and reserpine in mice by means of two stimulating substances. Acta Pharmacol Toxicol 14:138–147Google Scholar
  22. Koe BK (1976) Molecular geometry of inhibitors of the uptake of catecholamines and serotonin in synaptosomal preparations of rat brain. J Pharmacol Exp Ther 199:649–661Google Scholar
  23. Kokkinidis L, Anisman H (1978) Involvement of norepinephrine in startle arousal after acute and chronic d-amphetamine administration. Psychopharmacology 59:285–292Google Scholar
  24. Kokkinidis L, MacNeil EP (1982) Potentiation of d-amphetamine and l-dopa induced acoustic startle activity after long-term exposure to amphetamine. Psychopharmacology 78:331–335Google Scholar
  25. Kromer LF, Moore RY (1976) Cochlear nucleus innervation by central norepinephrine neurons in the rat. Brain Res 118:531–537Google Scholar
  26. Miczek KA, Yoshimura H (1982) Disruption of primate social behavior by d-amphetamine and cocaine: Differential anatognism by antipsychotics. Psychopharmacology 76:163–171Google Scholar
  27. Moore KE, Chiueh CC, Zeldes G (1977) Release of neurotransmitters from the brain in vivo by amphetamine, methylphenidate and cocaine. In: Ellinwood EH, Kilbey MH (eds) Cocaine and other stimulants. Plenum, New York pp 143–160Google Scholar
  28. Ritchie JM, Cohen PJ, Dripps RD (1970) Cocaine; Procaine and other synthetic local anaesthetics. In: Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics. Macmillan, Toronto, pp 371–402Google Scholar
  29. Roberts DCS, Corcoran ME, Fibiger HC (1977) On the role of ascending catecholamine systems in intravenous self-administration of cocaine. Pharmacol Biochem Behav 6:615–620Google Scholar
  30. Roberts DCS, Koob GF, Klonoff P, Fibiger HC (1980) Extinction and recovery of cocaine self-administration following 6-hydroxydopamine lesions of the nucleus accumbens. Pharmacol Biochem Behav 12:781–787Google Scholar
  31. Ross SF, Renyi AL (1967) Inhibition of the uptake of tritiated catecholamines by antidepressants and related agents. Eur J Pharmacol 2:181–186Google Scholar
  32. Scheel-Kruger J, Braestrup C, Nielson M, Golembiowska, K, Mogilnicka E (1977) Cocaine: Discussion on the role of dopamine in the biochemical mechanism of action. In: Ellinwood EH, Kilbey MH (eds) Cocaine and other stimulants. Plenum, New York, pp 373–407Google Scholar
  33. Smith CB (1963) Enhancement by reserpine and α-methyl dopa of the effects of d-amphetamine upon the locomotor activity of mice. J Pharmacol Exp Ther 142:343–350Google Scholar
  34. Spyraki C, Fibiger HC, Phillips AG (1982) Cocaine-induced place preference conditioning: Lack of effects of neuroleptics and 6-hydroxydopamine lesions. Brain Res 253:195–203Google Scholar
  35. Stolk JM, Rech RH (1968) Enhanced stimulant effects of d-amphetamine in rats treated chronically with reserpine. J Pharmacol Exp Ther 163:75–83Google Scholar
  36. Swanson LW, Hartman BK (1975) The central adrenergic system. An immunofluorescence study of the location of cell bodies and their efferent connections in the rat utilizing dopamine β-hydroxylase as a marker. J Comp Neurol 163:467–506Google Scholar
  37. Wallach MB, Gershon S (1972) The induction and antagonism of central nervous system stimulant-induced stereotyped behavior in the cat. Eur J Pharmacol 18:22–26Google Scholar
  38. Weiss GT, Davis M (1976) Automated system for acquisition and reduction of startle response data. Pharmacol Biochem Behav 4:713–720Google Scholar
  39. Willner JH, Samach M, Angrist B, Wallach MB, Gershon S (1970) Drug-induced stereotyped behavior and its antagonism in dogs. Commun Behav Biol 5:135–141Google Scholar
  40. Wiszniowska-Szafraniec GL, Danek K, Reichenberg K, Vetulani J (1982) Facilitation by adrenolytics of apomorpine gnawing behavior: Depression of threshold apomorphine concentration in the striatum of the rat. Pharmacol Biochem Behav 19:19–21Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • Michael Davis
    • 1
    • 2
  1. 1.Yale University School of MedicineNew HavenUSA
  2. 2.The Ribicoff Research Facilities of the Connecticut Mental Health CenterNew HavenUSA

Personalised recommendations