Four rats were subjected to chained fixed-ratio (FR), fixed-interval (FI) schedules of reinforcement (chain FR 5 FI). A FR schedule at one lever produced a discriminative stimulus (i.e., light) associated with an FI schedule of primary reinforcement (water) at the second response lever. The FR schedule was kept constant, whereas the FI length was changed from 10 to 60 s under five different experimental conditions. Increases in the FI length resulted in increases in pre-ratio pauses, but pauses in the FI tended to be a constant percentage of FI length. Data from this experiment indicate that pre-ratio pauses are also a function of the interreinforcement interval (IRI). Data from three experiments with chained FR 5 FI 60-s schedules indicate that pausing in the FI component of chained FR FI schedules with the FI as the second component of the chain may tend to disappear as the IRI duration increases.

Ten rats were submitted to chained fixed-ratio (FR), fixed-interval (FI) schedules of reinforcement. A FR schedule at one lever produced a discriminative stimulus associated with a FI 60-s schedule of primary reinforcement (water) at the second response lever. In Experiment 1, the FI schedule was kept constant while the FR requirement was changed from one to seven responses under five different experimental conditions for five rats. Increases in the FR requirement resulted in increases in post-reinforcement pauses but also decreases in pauses in the FI schedule. Using another five rats, Experiment 2 tested the hypothesis that short pauses in the FI schedule result from the use of the chained schedules procedure. Baseline was a FI 80-s schedule. In the second condition, chained FR 1 FI 80-s schedules were programmed. The third condition was a return to baseline. In baselines 1 and 2, the FI pause was compatible with the literature but decreased considerably when a chained schedule was used. The present results support the hypothesis that the time between primary reinforcement presentations dominates the control of FI pauses over control by the onset of a discriminative stimulus.

A ativação farmacológica dos receptores 5-HT2C induz comportamentos de defesa em modelos animais. O estudo busca investigar se o bloqueio seletivo de receptores 5-HT2C no hipocampo ventral (HV) previne comportamentos defensivos induzidos por um agonista de receptor 5-HT2C administrado perifericamente em ratos expostos ao labirinto em cruz elevado (LCE). Quinze minutos após injeções intraperitoniais (IP, 1ml/kg) do agonista 5-HT2C WAY-161503, ratos foram microinjetados bilateralmente no HV com o antagonista seletivo de receptores 5-HT2C SB-242084 (0, 0,1, 0,5 ou 1.5μg). Dez minutos após, cada animal foi exposto ao LCE para o registro de categorias de ansiedade. Injeções sistêmicas do WAY-161503 reduziram seletivamente as explorações nos braços abertos e aumentaram padrões de avaliação de risco. Esse efeito foi atenuado de maneira dose-dependente pela microinjeção de SB-242084 no HV, confirmando a ação ansiogênica de agonistas 5-HT2C e sugerindo que esse perfil comportamental seja mediado, pelo menos em parte, por receptores 5-HT2C do HV.

Pharmacological 5-HT2C receptor activation induces defensive behaviors in several animal models of anxiety. The present study investigated whether the selective blockade of 5-HT2C receptors in the ventral hippocampus (VH) prevents defensive behaviors induced by a 5-HT2C agonist administered systemically in rats exposed to the elevated plus-maze (EPM). Fifteen minutes after intraperitonial (IP, 1ml/kg) injections of the selective 5-HT2C receptor agonist WAY-161503 (3 mg/kg), rats were bilaterally microinjected with the selective 5-HT2C antagonist SB-242084 (0, 0.1, 0.5 or 1.5μg) into the VH. Ten minutes after, each animal was exposed to the EPM for measuring classical and ethological anxiety measures. IP WAY-161503 injections selectively decreased open-arm exploration while increasing risk-assessment. This anxiogenic-like action was dose-dependently attenuated by intra-VH SB-242084 microinjections. These results not only further confirm the anxiogenic-like action of 5-HT2C agonists, but also suggest that this behavioral profile might be mediated at least in part by VH 5-HT2C receptors.

This study investigated the behavioral effects in the forced swim test (FST) and the elevated plus-maze (EPM) of acute administration of WAY 161503 ([4aR]-8,9-dichloro-2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]quinoxalin-5[6 H]-one), a selective 5-HT2C receptor agonist with putative antidepressant-like properties. Fifteen minutes after intraperitoneal (i.p.) injections of either WAY 161503 (1, 3 and 10 mg/kg) or saline, naive male Wistar rats were exposed to the EPM for 5 min to assess classical and ethological anxiety-like measures. Immediately after EPM exposure, each animal was exposed to the FST, and the latency to the first episode of immobility was recorded (trial session). Twenty-four hours later, the rats were reexposed to a second EPM-FST exposure sequence (test session for FST) under the effect of the same pharmacological treatment. The two lowest WAY 161503 doses selectively reduced open-arm exploration and increased risk-assessment without affecting locomotor activity. This selective anxiogenic-like effect was observed in both the first and second EPM exposures. The highest WAY 161503 dose produced robust locomotor impairment. In the FST, the same WAY 161503 doses significantly increased the latency to the first immobility in the test session, a behavioral profile that suggests an antidepressant-like action. These results further support the involvement of 5-HT2C receptors in the mediation of anxiety and suggest an intricate relationship between anxiogenic- and antidepressant-like actions.