Septal co-infusions of glucose with the benzodiazepine agonist chlordiazepoxide impair memory, but co-infusions of glucose with the opiate morphine do not

Abstract

We have found repeatedly that medial septal (MS) infusions of glucose impair memory when co-infused with the gamma-amino butyric acid (GABA) agonist muscimol. The present experiments sought to determine whether the memory-impairing effects of this concentration of glucose would generalize to another GABA(A) receptor agonist and to an agonist from another neurotransmitter system that is known to impair memory. Specifically, we determined whether the dose of glucose that produces memory deficits when combined with muscimol in the MS would also impair memory when co-infused with the GABA(A) receptor modulator chlordiazepoxide (CDP) or the opiate morphine. Male Sprague-Dawley rats were given MS co-infusions and then 15 min later tested for spontaneous alternation or given shock avoidance training (retention tested 48 h later). The results showed that MS infusions of the higher dose of glucose with morphine did not produce memory deficits, whereas, the performance of rats given MS co-infusions of CDP with glucose was impaired. These findings suggest that the memory-impairing effects of brain glucose administration may involve an interaction with the GABA(A) receptor.

Figure 1

Schematic illustration of coronal sections of the rat brain showing the approximate location of MS infusion sites in Experiment 1. Atlas plates were adapted from Paxinos and Watson (1998).

Figure 2

Figure 2A. MS co-infusions of glucose with morphine did not significantly decrease mean (+/− S.E.M.) percent alternation scores (p > .05 vs. PBS). Figure 2B. There were no significant effects of any of the manipulations on the mean (+/− S.E.M.) number of arm entries (p > .05 vs. PBS).

Figure 2

Figure 2A. MS co-infusions of glucose with morphine did not significantly decrease mean (+/− S.E.M.) percent alternation scores (p > .05 vs. PBS). Figure 2B. There were no significant effects of any of the manipulations on the mean (+/− S.E.M.) number of arm entries (p > .05 vs. PBS).

Figure 3

Figure 3A. There were no significant effects of any of the manipulations on the mean (+/− S.E.M.) number of trials to criterion (p > .05 vs. PBS). Figure 3B. MS infusions of morphine (8 nmol) decreased median (+/− I.Q.) retention latencies (*p < .05 vs. PBS). MS infusions of glucose did not produce deficits when combined with subeffective doses of morphine (p > .05 vs. PBS).

Figure 3

Figure 3A. There were no significant effects of any of the manipulations on the mean (+/− S.E.M.) number of trials to criterion (p > .05 vs. PBS). Figure 3B. MS infusions of morphine (8 nmol) decreased median (+/− I.Q.) retention latencies (*p < .05 vs. PBS). MS infusions of glucose did not produce deficits when combined with subeffective doses of morphine (p > .05 vs. PBS).

Figure 4

Figure 4A. MS infusions of CDP (30 nmol) significantly decreased mean (+/− SEM) percent alternation scores (*p < .05 vs. saline). More importantly, MS co-infusions of CDP (15 nmol) with glucose, at doses that had no affect on their own (p > .05 vs. saline), significantly decreased mean percent alternation scores (*p < .05 vs. saline). Figure 4B. MS infusions of CDP did not significantly impair mean (+/−S.E.M.) number of arm entries (p > .05 vs. saline).

Figure 4

Figure 4A. MS infusions of CDP (30 nmol) significantly decreased mean (+/− SEM) percent alternation scores (*p < .05 vs. saline). More importantly, MS co-infusions of CDP (15 nmol) with glucose, at doses that had no affect on their own (p > .05 vs. saline), significantly decreased mean percent alternation scores (*p < .05 vs. saline). Figure 4B. MS infusions of CDP did not significantly impair mean (+/−S.E.M.) number of arm entries (p > .05 vs. saline).

Figure 5

Figure 5A. MS infusions of CDP did not significantly impair median (+/−I.Q.) trials to criterion (p > .05 vs. saline). Figure 5B. MS infusions of CDP did not significantly impair median (+/−I.Q.) retention latencies (p > .05 vs. saline).

Figure 5

Figure 5A. MS infusions of CDP did not significantly impair median (+/−I.Q.) trials to criterion (p > .05 vs. saline). Figure 5B. MS infusions of CDP did not significantly impair median (+/−I.Q.) retention latencies (p > .05 vs. saline).