EXCITATORY CARDIOVASCULAR AND RESPIRATORY EFFECTS OF BACLOFEN IN INTACT RATS

The rat has become the preferred animal model for study of the central control of the cardiorespiratory system. However, data in the literat ure suggest that the role of GABA(B) receptors in control of the respi ratory timing may be different in rats from that in other species. The refore in this study we investigated cardiorespiratory effects of repe ated injections of 0.5 nM baclofen and 50 nM CGP35348, GABA(B) recepto r agonist and antagonist, respectively, applied into the fourth ventri cle of urethane-anesthetized intact, spontaneously breathing Wistar ra ts. Baclofen increased arterial blood pressure (ABP), heart rate, insp iratory time (Ti), and the rate of rise (Di/t) and peak amplitude of t he integrated diaphragmatic EMG (Di). Expiration (Te) was unaffected. CGP35348 reversed the ABP and Di effects of baclofen and decreased Di/ t and Te below their control values, whereas Ti remained prolonged. Th ese excitatory effects of baclofen are consistent with previously repo rted effects of low i.v. doses of baclofen in cats, and suggest that G ABA(B) receptors may modulate the depth and duration of inspiration. W e conclude that the intact rat represents a suitable animal model for investigations of the integrated control of cardiorespiratory function s. To our knowledge this is the first investigation reporting excitato ry effects of GABA(B) receptor stimulation on inspiratory activity in rats. The depressant effects of baclofen on the respiratory rhythm rep orted in the rat ''isolated'' brain in situ, and the neonatal rat brai nstem - spinal cord in vitro seem to be unique for those specific prep arations. Key