Behavioural Brain Research 160 (2005) 99–106 Postnatal caffeine exposure: effects on motor skills and locomotor activity during ontogenesis Jana Tchekalarova a,b,∗ , Hana Kubova b , Pavel Mareˇ s b a Laboratory of Experimental Psychopharmacology, Institute of Physiology, Acad. G. Bonchev Str., Bl. 23, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria b Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic Received 21 September 2004; received in revised form 12 November 2004; accepted 15 November 2004 Available online 28 December 2004 Abstract It has been shown that long-term postnatal caffeine treatment results in biochemical and behavioral changes persisting into adulthood. The effects of postnatal chronic exposure to this methylxanthine on motor skills and locomotor activity were studied with a battery of motor and behavioral tests (negative geotaxis test, wire mesh ascending test, jumping down with a choice test, bar holding test, rotarod test and open field test) in rats during development. Pup rats were daily injected with caffeine (10 mg/kg or 20 mg/kg, s.c.) during postnatal days 7–11 (the P7 group) and/or 13–17 (the P13 group). Motor impairments occurred in 15-, 18- and 21-day-old rats treated with caffeine at P7–P11, whereas, pups exposed to caffeine from P13 to P17 exhibited worse performance only in the bar holding test at the age of 18 days. The P7 group was hyperactive in an open field during the whole period of testing. In contrast, the P13 group showed a decrease of motor activity at postnatal days 25 and 32. In conclusion, postnatal treatment of rats with caffeine leads to impairments of motor skills and changes in locomotor activity. The results are dependent at the developmental stages at caffeine administration as well as at age when tests are performed. © 2004 Elsevier B.V. All rights reserved. Keywords: Caffeine; Ontogenesis; Rats; Motor skills; Locomotor activity 1. Introduction Caffeine is one of the most often consumed CNS stim- ulants. The following main mechanisms of action of this methylxanthine have been proposed [25]: at high mil- limolar concentrations caffeine exerts mobilization of in- tracelullar calcium and inhibition of specific phosphodi- esterases, whereas, at physiological micromolar concentra- tions it appears to be a competitive antagonist of the tonic depressant effect of endogenous adenosine. It is generally assumed that behavioral stimulatory effect of caffeine is re- alized through a blockade of central adenosine A 1 and A 2A receptors, respectively. The effects of chronic administration of caffeine on the amount and function of central adenosine ∗ Corresponding author. Tel.: +359 979 2172; fax: +359 2 719 109. E-mail address: jane tch@yahoo.com (J. Tchekalarova). A 1 receptors have been studied using a variety of schedules concerning dose and time course [3,5,10,17]. In most stud- ies, the increase in the number of adenosine receptors is not accompanied by a modification in the affinity [3,5,10]. Al- though, long-term treatment with adenosine receptor antago- nists has effects that resemble the acute effects of respective agonists, an alteration in the number of adenosine receptors is not obligatory for functional change [25]. There are many reports demonstrating durable behav- ioral changes as a result of perinatal and postnatal long- term caffeine exposure [9,14,18]. Furthermore, when rats are exposed to 20 mg/kg/day caffeine during gestation and the first 13 weeks of postnatal life, levels of DNA, proteins, and Zn can be changed differently in individual brain ar- eas [24]. These alterations persisted for several months after withdrawal of the methylxanthine. Perinatal caffeine expo- sure also induces biochemical changes, such as modifica- 0166-4328/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2004.11.018