Beta1-adrenoreceptors of the CA1 area mediate morphine-modified state-dependent memory in rats

In our study, we investigated the effects of intra-CA1 microinjections of a selective β1-adrenoreceptor antagonist, betaxolol, on state-dependent memory induced by morphine. A step-through passive avoidance task was used to assess memory retrieval. Male Wistar rats were bilaterally implanted with chronic cannulas in the CA1 regions of the dorsal hippocampus by stereotaxic surgery seven days before training. Each animal was tested 24 h after training to measure the step-through latency and the time spent in a dark chamber of the apparatus. Post-training intra-CA1 administrations of different doses of morphine (5 and 7.5 mg/kg, s.c.) decreased memory retrieval in the retention test (morphine-induced amnesia). The effect of post-training injections of 7.5 mg/kg morphine on retrieval was reversed by pre-test injection of the same dose of morphine. This phenomenon is named morphine state-dependent memory. The results also showed that pre-test intra-CA1 microinjection of ineffective low doses of betaxolol (0.125 and 0.25 mg/rat) inhibited morphine-induced state-dependent memory retrieval. Taken together, our results suggest that the CA1 may be potentially critical for morphine state-dependent memory, and the β1-adrenergic receptor mechanism(s) interact with the opioidergic system in the modulation of this type of memory in the CA1.