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Amygdala lesions block the effect of cocaine on memory in mice
BRAIN RESEARCH ELSEVIER
Brain Research 713 (1996) 286-289
Research report
Amygdala lesions block the effect of cocaine on memory in mice Vincenzo Cestari a,b,* Andrea Mele ", Alberto Oliverio a,b Claudio Castellano b " Dipartimento di Genetica e Biologia Molecolare, Uniuersith degli Studi di Roma 'La Sapienza ', P.le A. Moro 5, 00185 Roma, Italy b Istituto di Psicobiologia e Psicofarmacologia (C.N.R.), Via Reno 1, 00198 Roma, Italy
Accepted 5 December 1995
Abstract
Post-training cocaine intraperitoneal administration enhanced memory consolidation in unoperated and sham-lesioned mice tested in a
one-trial inhibitory avoidance task. Bilateral electrolytical amygdala lesions blocked this effect. The results are interpreted in terms of involvement of neurotransmitter, and in particular dopaminergic, systems in the effects of cocaine on memory.
Keywords: Cocaine; Memory; Amygdala; Lesion; One-trial inhibitory avoidance
I. Introduction Experiments carried out in the recent years have shown that cocaine administered post-training enhances retention in mice and rats tested in one-trial inhibitory avoidance and active avoidance tasks [8,10,14]. Some researches have studied the mechanisms through which cocaine enhances memory consolidation. It has been thus observed in mice that this effect is mediated through the dopaminergic system. In fact, in the C 5 7 B L / 6 (C57) strain of mice, whose retention is enhanced by post-training cocaine administration, the effect of this drug was antagonized by pretreatment with the D t or D 2 dopamine (DA) receptor antagonists SCH 23390 and (-)-sulpiride [14]. Amygdala is an important brain region which mediates the effects on memory exerted by several drugs and hormones. It has in fact been demonstrated that this structure is involved in the memory modulation of drugs affecting opiate, adrenergic and GABAergic receptor systems [1,7,9,11]. An important catecholaminergic input to amygdala has been shown by histochemical data [6]. Amygdala, and in particular the central nucleus, receives a heavy dopaminergic input. This evidence is supported by biochemical studies [5]. In the present research we have studied the effects of electrolytic lesions to the amygdala on the enhancing effect on memory exerted by cocaine. Cocaine was admin-
*
Corresponding author.
11006-8993/96/$15.00 © 1996 Elsevier Science SSDI 001)6-8993(95)01556-6
istered immediately after training to CD1 mice, which were tested in a one-trial inhibitory avoidance task.
2. Materials and methods
2.1. Subjects The subjects were male CD1 mice (Charles River Laboratories, Como, Italy). They weighed approximately 25 g, were caged in groups of eight with food and water available ad libitum and were maintained on a 12:12 h light/dark cycle (lights on at 07.00 h) at a constant temperature of 21°C for 2 weeks prior to the surgical treatments and subsequent behavioral experiments.
2.2. Surgery Mice in some groups received bilateral electrolytic lesions of the amygdala while controls for the surgery received sham operations. Mice were anesthetized with chloral hydrate (400 m g / k g ) and placed in a Narishige stereotaxic apparatus with mouse adaptor. The scalp was incised and retracted and hole was drilled through the skull at point above the intended site of lesion. A stainless steel electrode (0.2 mm diameter), that was insulated except at the tip, was inserted into the targeted brain region by means of the stereotaxic apparatus and with lambda and bregma in the same horizontal plane. The stereotaxic coordinates (in mm) were as follows: - 1.8 P, 3.1 L and 4.0 V.
V. Cestari et al. / Brain Research 713 (1996) 286-289
i
Bregma
-1.6
287
turned around, the door leading to the dark compartment was opened. When the mouse had stepped with all four paws into the dark side, the door was closed, a foot-shock (0.2 mA, 50 Hz, 1 s) was delivered, and the latency to step through was recorded. The mouse was removed from the apparatus and injected. Retention was tested 24 h later following a similar procedure, except that no shock was administered. A maximum step-through latency of 180 s was considered.
2.5. Statistics
regma
-1,8
The step-through latencies of the unoperated mice given different drug treatment were analyzed with one-way ANOVAs. Retention test latencies of the lesioned and sham-lesioned groups given control and drug injections were assessed with two-way ANOVAs the factors being lesion (two levels: sham and lesion) and treatment (three levels: saline, 2.5 and 5 m g / k g of cocaine). Individual between-group comparisons, when appropriate, were carried out by post hoc test (Duncan multiple-range test).
2.6. Drug administration
regma
-2.0
Fig. 1. Representative bilateral lesions of amygdala.
The lesions were induced by delivering a 2.5-mA anodal current through the electrode for 2 s using a cathode taped to the animal's tail. The procedures were the same for sham operations except that no current was delivered. At the completion of the surgery, the scalp was sutured closed. The mice were allowed to recover from the surgery for one week prior to behavioral testing.
2.3. Histology At the completion of the behavioral experiments the lesioned and the sham-operated animals were sacrificed under chloral anesthesia and their brains were fixed in formalin (10% solution), sectioned coronally (60 /xm) and stained with Toluidine blue according to the Nissl method. Fig. 1 shows typical amygdala lesions.
Immediately after training the mice were injected intraperitoneally (i.p.) with a saline (0.9% NaC1) solution or a cocaine solution. The unoperated animals received different doses of cocaine (0, 1, 2.5, 5, 10 m g / k g ) , while the sham-lesioned and amygdala-lesioned mice received saline, or cocaine (2.5, 5 m g / k g ) . Cocaine was dissolved in saline and injected in a volume of 10 m l / k g .
3. R e s u l t s
The retention test response of unoperated mice given immediate post-training injections of cocaine are shown in ~" 200
Z [... .<
160'
120
O l~l
80
40 Z <
2.4. Behavioral procedures
o 0
Mice were trained on a step-through inhibitory avoidance apparatus, as previously described [12]. On the training day each mouse was placed in the light compartment, facing away from the dark compartment. When the mouse
1 Cocaine
2.5
5
10
(mg/kg)
Fig. 2. D o s e - r e s p o n s e effects of post-training injections of cocaine on retention in unoperated mice. * P < 0.01 vs. saline- and cocaine (1 m g / k g ) - i n j e c t e d mice.
288
V. Cestari et al. / B r a i n Research 713 (1996) 286-289 []
180
UNOPERATED
[] SnAM Z
150
•
I
LESIONED
.< 120 O
90 ~
" [..
60
Z: .<
30
0
0
0 Cocaine
2.5
5
(mg:kg)
Fig. 3. Dose-response effects of post-training injections of cocaine on retention in sham-lesioned (SHAM) and amygdala-lesioned (LESIONED) mice. * P < 0.01 vs. thc corresponding sham-lesioned groups (dotted columns) and the unoperated saline-injected mice (white column).
Fig. 2. As can be seen, cocaine improved retention (F(4,35) = 81.36, P < 0.001) in a dose-dependent fashion. Duncan's multiple range tests indicate that all groups differed from each other except two groups (saline and cocaine 1 m g / k g ) . On the training trial, all step-through latencies were 10 s or less. The training latencies of animals in the lesion groups were highly comparable to those of unoperated controls. The retention latencies of the groups with lesions of the amygdala were lower than those of the sham-lesioned and unoperated controls ( F ( 2 , 2 1 ) = 35.25, P < 0.001). Moreover, no significant differences were found between sham-lesioned and unoperated control groups. The effects of immediate post-training injections of cocaine on the retention performance of amygdala-lesioned and sham-lesioned mice are shown in Fig. 3. As can be seen, the amygdala lesions blocked the improving effects on the retention performance of the administration of two doses of cocaine (2.5 and 5 m g / k g ) . In fact, in the sham-operated animals cocaine improved in a dose-dependent fashion the retention performance. There were a main effect of the lesion ( F ( 1 , 4 2 ) = 515.49, P < 0.001) and a main effect of the treatment (F(2,42) = 39.09, P < 0.001). The interaction between the two factors was also significant (F(2,42) = 40.68, P < 0.001)
ory enhancement following post-training cocaine administration has been previously demonstrated in CFW mice [8] and in mice belonging to the C57 strain [14] tested in one-trial inhibitory avoidance tasks. As concerns the amygdala lesions, it must be considered that they produced impairment of retention performance. Moreover, the retention latencies of each lesioned group were significantly lower than those of the sham controls. Finally, lesions effects on locomotor activity can be excluded, since the step-through latencies of the lesioned mice on the training day were comparable to those of the control groups (10 s or less). These results are consistent with those of previous investigations [1,3]. A number of hypotheses can be made concerning the results of the present research. It must be considered that biochemical data show the existence of a dopaminergic input to the amygdala [2,5]. Furthermore it has been shown that dopaminergic mechanisms are involved in the effects of cocaine on memory consolidation. The memory-enhancing effect of cocaine was in fact antagonized by pretreatment with D 1 or D~ receptor antagonist in previous researches [14]. The present results obtained in amygdala lesioned mice can thus be interpreted on the basis of the above reported evidences. In fact, the data might suggest a block of the dopaminergic input to the amygdala in the lesioned groups of animals. However, it must be considered that a number of studies have reported that retention can be influenced by post-training intra-amygdala injections of drugs which affect several neurotransmitter systems. It has been shown, for example, that treatments affecting noradrenergic (NA) and opioid peptidergic receptors within the amygdala can modulate memory processes [9,11]. Further, some experiments have demonstrated that the effects of systemic administration of GABAergic drugs are blocked by lesions of this structure [1]. It must be stressed that interaction between DA and endogenous opioids in memory consolidation in the mouse has been envisaged [4], while data indicating D A - G A B A interaction at neurochemical and behavioral level have been reported [13,14]. Thus a possible involvement of the NA system or an interaction among DA and other neurotransmitter systems in the effects of cocaine on memory remains, at the light of the above cited evidences, an open question. It is in every case clear, from the results of the present research, that amygdala is a critical structure in mediating the modulation of cocaine in memory processes. Further researches are now in progress to better clarify the mechanisms underlying the observed effects.
4. Discussion From the results of the present research it is evident that post-training cocaine administration dose-dependently enhanced retention performance of unoperated CD1 mice tested in a one-trial inhibitory avoidance task. Moreover this effect was blocked by lesions of the amygdala. Mem-
Acknowledgements We thank Dr. Clelia Rossi-Arnaud for her helpful suggestions during the preparation of the manuscript.
V. Cestari et al. / Brain Research 713 (1996) 286-289
References [1] Ammassari-Teule, M., Pavone, F., Castellano, C. and McGaugh, J.L., Amygdala and dorsal hippocampus lesions block the effescts of GABAergic drugs on memory storage, Brain Res., 551 (1991) 104-109. [2] Brownstein, M.J., Saavedra, J.M. and Palkonts, M., Norepinephrine and dopamine in the limbic system of the rat, Brain Res., 79 (1974) 431-436. [3] Cahill, L. and McGaugh, J.L., Amygdaloid complex lesions differentially affect retention of tasks using appetitive and aversive reinforcement, Behav. Neurosci., 104 (1991) 532-543. [4] Castellano, C. and Puglisi-Allegra, S., In E. Endocri (Ed.), Neuropeptides and Psychosomatic Processes, Publishing House of the Hungarian Academy of Science, Budapest, 1983, pp. 111-117. [5] Enson, P.C., Bjorklund, A., Lindvall, O. and Paxinos, G., Contribution of different afferent pathways to the catecholamine and 5-hydroxytryptamine innervation of the amygdala: A neurochemical and histochemical study, Neuroscience, 4 (1979) 1347-1357. [6] Fuxe, K., Evidence for the existence of monoamine neurones in the central nervous system. IV. Distribution of monoamine nerve terminals in the central nervous system, Acta Physiol. Scand., 64 (Suppl. 247) (1965) 36-85. [7] Gallagher, M. and Kapp, B.S., Manipulation of opiate activity in the amygdala alters memory processes, Life Sci., 23 (1978) 1973-1978.
289
[8] Introini-Collison, I.B. and McGaugh, J.L., Cocaine enhances memory storage in mice, Psychopharmacology, 99 (1989) 537-541. [9] Introini-Collison, I.B., Nagahara, A.H. and McGaugh, J.L., Memory-enhancement with intra-amygdala post-training naloxone is blocked by concurrent administration of propanolol, Brain Res., 476 (1989) 94-101. [10] Janak, P.H., Keppel, G. and Martinez Jr., J.L., Cocaine enhances retention of avoidance conditioning in rats, Psychopharmacology, 106 (1992) 383-387. [11] Liang, K.C., Juler, R. and McGaugh, J.L., Modulating effects of post-training epinephrine on memory: involvement of the amygdala noradrenergic system, Brain Res., 368 (1986) 125-133. [12] McGaugh, J.L. and Landfield, P.W., Delayed development of amnesia following electro-convulsive shock, Physiol. Behae., 5 (1970) 1109-1113 [13] Puglisi-Allegra, S., Mack, G., Oliverio, A. and Mandel, P., Effects of apomorphine and sodium di-n-propylacetate on the aggressive behavior of three strain of mice, Prog. Neuropsychopharmacol., 3 (1979) 491-502. [14] Puglisi-Allegra, S., Cestari, V., Cabib, S. and Castellano, C., Straindependent effects of post-training cocaine or nomifensine on memory storage involve both D I and D 2 dopamine receptors, Psychopharmacology, 115 (1994) 157-162.
Brain Research 713 (1996) 286-289
Research report
Amygdala lesions block the effect of cocaine on memory in mice Vincenzo Cestari a,b,* Andrea Mele ", Alberto Oliverio a,b Claudio Castellano b " Dipartimento di Genetica e Biologia Molecolare, Uniuersith degli Studi di Roma 'La Sapienza ', P.le A. Moro 5, 00185 Roma, Italy b Istituto di Psicobiologia e Psicofarmacologia (C.N.R.), Via Reno 1, 00198 Roma, Italy
Accepted 5 December 1995
Abstract
Post-training cocaine intraperitoneal administration enhanced memory consolidation in unoperated and sham-lesioned mice tested in a
one-trial inhibitory avoidance task. Bilateral electrolytical amygdala lesions blocked this effect. The results are interpreted in terms of involvement of neurotransmitter, and in particular dopaminergic, systems in the effects of cocaine on memory.
Keywords: Cocaine; Memory; Amygdala; Lesion; One-trial inhibitory avoidance
I. Introduction Experiments carried out in the recent years have shown that cocaine administered post-training enhances retention in mice and rats tested in one-trial inhibitory avoidance and active avoidance tasks [8,10,14]. Some researches have studied the mechanisms through which cocaine enhances memory consolidation. It has been thus observed in mice that this effect is mediated through the dopaminergic system. In fact, in the C 5 7 B L / 6 (C57) strain of mice, whose retention is enhanced by post-training cocaine administration, the effect of this drug was antagonized by pretreatment with the D t or D 2 dopamine (DA) receptor antagonists SCH 23390 and (-)-sulpiride [14]. Amygdala is an important brain region which mediates the effects on memory exerted by several drugs and hormones. It has in fact been demonstrated that this structure is involved in the memory modulation of drugs affecting opiate, adrenergic and GABAergic receptor systems [1,7,9,11]. An important catecholaminergic input to amygdala has been shown by histochemical data [6]. Amygdala, and in particular the central nucleus, receives a heavy dopaminergic input. This evidence is supported by biochemical studies [5]. In the present research we have studied the effects of electrolytic lesions to the amygdala on the enhancing effect on memory exerted by cocaine. Cocaine was admin-
*
Corresponding author.
11006-8993/96/$15.00 © 1996 Elsevier Science SSDI 001)6-8993(95)01556-6
istered immediately after training to CD1 mice, which were tested in a one-trial inhibitory avoidance task.
2. Materials and methods
2.1. Subjects The subjects were male CD1 mice (Charles River Laboratories, Como, Italy). They weighed approximately 25 g, were caged in groups of eight with food and water available ad libitum and were maintained on a 12:12 h light/dark cycle (lights on at 07.00 h) at a constant temperature of 21°C for 2 weeks prior to the surgical treatments and subsequent behavioral experiments.
2.2. Surgery Mice in some groups received bilateral electrolytic lesions of the amygdala while controls for the surgery received sham operations. Mice were anesthetized with chloral hydrate (400 m g / k g ) and placed in a Narishige stereotaxic apparatus with mouse adaptor. The scalp was incised and retracted and hole was drilled through the skull at point above the intended site of lesion. A stainless steel electrode (0.2 mm diameter), that was insulated except at the tip, was inserted into the targeted brain region by means of the stereotaxic apparatus and with lambda and bregma in the same horizontal plane. The stereotaxic coordinates (in mm) were as follows: - 1.8 P, 3.1 L and 4.0 V.
V. Cestari et al. / Brain Research 713 (1996) 286-289
i
Bregma
-1.6
287
turned around, the door leading to the dark compartment was opened. When the mouse had stepped with all four paws into the dark side, the door was closed, a foot-shock (0.2 mA, 50 Hz, 1 s) was delivered, and the latency to step through was recorded. The mouse was removed from the apparatus and injected. Retention was tested 24 h later following a similar procedure, except that no shock was administered. A maximum step-through latency of 180 s was considered.
2.5. Statistics
regma
-1,8
The step-through latencies of the unoperated mice given different drug treatment were analyzed with one-way ANOVAs. Retention test latencies of the lesioned and sham-lesioned groups given control and drug injections were assessed with two-way ANOVAs the factors being lesion (two levels: sham and lesion) and treatment (three levels: saline, 2.5 and 5 m g / k g of cocaine). Individual between-group comparisons, when appropriate, were carried out by post hoc test (Duncan multiple-range test).
2.6. Drug administration
regma
-2.0
Fig. 1. Representative bilateral lesions of amygdala.
The lesions were induced by delivering a 2.5-mA anodal current through the electrode for 2 s using a cathode taped to the animal's tail. The procedures were the same for sham operations except that no current was delivered. At the completion of the surgery, the scalp was sutured closed. The mice were allowed to recover from the surgery for one week prior to behavioral testing.
2.3. Histology At the completion of the behavioral experiments the lesioned and the sham-operated animals were sacrificed under chloral anesthesia and their brains were fixed in formalin (10% solution), sectioned coronally (60 /xm) and stained with Toluidine blue according to the Nissl method. Fig. 1 shows typical amygdala lesions.
Immediately after training the mice were injected intraperitoneally (i.p.) with a saline (0.9% NaC1) solution or a cocaine solution. The unoperated animals received different doses of cocaine (0, 1, 2.5, 5, 10 m g / k g ) , while the sham-lesioned and amygdala-lesioned mice received saline, or cocaine (2.5, 5 m g / k g ) . Cocaine was dissolved in saline and injected in a volume of 10 m l / k g .
3. R e s u l t s
The retention test response of unoperated mice given immediate post-training injections of cocaine are shown in ~" 200
Z [... .<
160'
120
O l~l
80
40 Z <
2.4. Behavioral procedures
o 0
Mice were trained on a step-through inhibitory avoidance apparatus, as previously described [12]. On the training day each mouse was placed in the light compartment, facing away from the dark compartment. When the mouse
1 Cocaine
2.5
5
10
(mg/kg)
Fig. 2. D o s e - r e s p o n s e effects of post-training injections of cocaine on retention in unoperated mice. * P < 0.01 vs. saline- and cocaine (1 m g / k g ) - i n j e c t e d mice.
288
V. Cestari et al. / B r a i n Research 713 (1996) 286-289 []
180
UNOPERATED
[] SnAM Z
150
•
I
LESIONED
.< 120 O
90 ~
" [..
60
Z: .<
30
0
0
0 Cocaine
2.5
5
(mg:kg)
Fig. 3. Dose-response effects of post-training injections of cocaine on retention in sham-lesioned (SHAM) and amygdala-lesioned (LESIONED) mice. * P < 0.01 vs. thc corresponding sham-lesioned groups (dotted columns) and the unoperated saline-injected mice (white column).
Fig. 2. As can be seen, cocaine improved retention (F(4,35) = 81.36, P < 0.001) in a dose-dependent fashion. Duncan's multiple range tests indicate that all groups differed from each other except two groups (saline and cocaine 1 m g / k g ) . On the training trial, all step-through latencies were 10 s or less. The training latencies of animals in the lesion groups were highly comparable to those of unoperated controls. The retention latencies of the groups with lesions of the amygdala were lower than those of the sham-lesioned and unoperated controls ( F ( 2 , 2 1 ) = 35.25, P < 0.001). Moreover, no significant differences were found between sham-lesioned and unoperated control groups. The effects of immediate post-training injections of cocaine on the retention performance of amygdala-lesioned and sham-lesioned mice are shown in Fig. 3. As can be seen, the amygdala lesions blocked the improving effects on the retention performance of the administration of two doses of cocaine (2.5 and 5 m g / k g ) . In fact, in the sham-operated animals cocaine improved in a dose-dependent fashion the retention performance. There were a main effect of the lesion ( F ( 1 , 4 2 ) = 515.49, P < 0.001) and a main effect of the treatment (F(2,42) = 39.09, P < 0.001). The interaction between the two factors was also significant (F(2,42) = 40.68, P < 0.001)
ory enhancement following post-training cocaine administration has been previously demonstrated in CFW mice [8] and in mice belonging to the C57 strain [14] tested in one-trial inhibitory avoidance tasks. As concerns the amygdala lesions, it must be considered that they produced impairment of retention performance. Moreover, the retention latencies of each lesioned group were significantly lower than those of the sham controls. Finally, lesions effects on locomotor activity can be excluded, since the step-through latencies of the lesioned mice on the training day were comparable to those of the control groups (10 s or less). These results are consistent with those of previous investigations [1,3]. A number of hypotheses can be made concerning the results of the present research. It must be considered that biochemical data show the existence of a dopaminergic input to the amygdala [2,5]. Furthermore it has been shown that dopaminergic mechanisms are involved in the effects of cocaine on memory consolidation. The memory-enhancing effect of cocaine was in fact antagonized by pretreatment with D 1 or D~ receptor antagonist in previous researches [14]. The present results obtained in amygdala lesioned mice can thus be interpreted on the basis of the above reported evidences. In fact, the data might suggest a block of the dopaminergic input to the amygdala in the lesioned groups of animals. However, it must be considered that a number of studies have reported that retention can be influenced by post-training intra-amygdala injections of drugs which affect several neurotransmitter systems. It has been shown, for example, that treatments affecting noradrenergic (NA) and opioid peptidergic receptors within the amygdala can modulate memory processes [9,11]. Further, some experiments have demonstrated that the effects of systemic administration of GABAergic drugs are blocked by lesions of this structure [1]. It must be stressed that interaction between DA and endogenous opioids in memory consolidation in the mouse has been envisaged [4], while data indicating D A - G A B A interaction at neurochemical and behavioral level have been reported [13,14]. Thus a possible involvement of the NA system or an interaction among DA and other neurotransmitter systems in the effects of cocaine on memory remains, at the light of the above cited evidences, an open question. It is in every case clear, from the results of the present research, that amygdala is a critical structure in mediating the modulation of cocaine in memory processes. Further researches are now in progress to better clarify the mechanisms underlying the observed effects.
4. Discussion From the results of the present research it is evident that post-training cocaine administration dose-dependently enhanced retention performance of unoperated CD1 mice tested in a one-trial inhibitory avoidance task. Moreover this effect was blocked by lesions of the amygdala. Mem-
Acknowledgements We thank Dr. Clelia Rossi-Arnaud for her helpful suggestions during the preparation of the manuscript.
V. Cestari et al. / Brain Research 713 (1996) 286-289
References [1] Ammassari-Teule, M., Pavone, F., Castellano, C. and McGaugh, J.L., Amygdala and dorsal hippocampus lesions block the effescts of GABAergic drugs on memory storage, Brain Res., 551 (1991) 104-109. [2] Brownstein, M.J., Saavedra, J.M. and Palkonts, M., Norepinephrine and dopamine in the limbic system of the rat, Brain Res., 79 (1974) 431-436. [3] Cahill, L. and McGaugh, J.L., Amygdaloid complex lesions differentially affect retention of tasks using appetitive and aversive reinforcement, Behav. Neurosci., 104 (1991) 532-543. [4] Castellano, C. and Puglisi-Allegra, S., In E. Endocri (Ed.), Neuropeptides and Psychosomatic Processes, Publishing House of the Hungarian Academy of Science, Budapest, 1983, pp. 111-117. [5] Enson, P.C., Bjorklund, A., Lindvall, O. and Paxinos, G., Contribution of different afferent pathways to the catecholamine and 5-hydroxytryptamine innervation of the amygdala: A neurochemical and histochemical study, Neuroscience, 4 (1979) 1347-1357. [6] Fuxe, K., Evidence for the existence of monoamine neurones in the central nervous system. IV. Distribution of monoamine nerve terminals in the central nervous system, Acta Physiol. Scand., 64 (Suppl. 247) (1965) 36-85. [7] Gallagher, M. and Kapp, B.S., Manipulation of opiate activity in the amygdala alters memory processes, Life Sci., 23 (1978) 1973-1978.
289
[8] Introini-Collison, I.B. and McGaugh, J.L., Cocaine enhances memory storage in mice, Psychopharmacology, 99 (1989) 537-541. [9] Introini-Collison, I.B., Nagahara, A.H. and McGaugh, J.L., Memory-enhancement with intra-amygdala post-training naloxone is blocked by concurrent administration of propanolol, Brain Res., 476 (1989) 94-101. [10] Janak, P.H., Keppel, G. and Martinez Jr., J.L., Cocaine enhances retention of avoidance conditioning in rats, Psychopharmacology, 106 (1992) 383-387. [11] Liang, K.C., Juler, R. and McGaugh, J.L., Modulating effects of post-training epinephrine on memory: involvement of the amygdala noradrenergic system, Brain Res., 368 (1986) 125-133. [12] McGaugh, J.L. and Landfield, P.W., Delayed development of amnesia following electro-convulsive shock, Physiol. Behae., 5 (1970) 1109-1113 [13] Puglisi-Allegra, S., Mack, G., Oliverio, A. and Mandel, P., Effects of apomorphine and sodium di-n-propylacetate on the aggressive behavior of three strain of mice, Prog. Neuropsychopharmacol., 3 (1979) 491-502. [14] Puglisi-Allegra, S., Cestari, V., Cabib, S. and Castellano, C., Straindependent effects of post-training cocaine or nomifensine on memory storage involve both D I and D 2 dopamine receptors, Psychopharmacology, 115 (1994) 157-162.